Advertisement

Allergo Journal International

, Volume 27, Issue 3, pp 79–96 | Cite as

Respiratory virus-induced heterologous immunity

Part of the problem or part of the solution?
  • Emanuel Pusch
  • Harald Renz
  • Chrysanthi Skevaki
review

Abstract

Purpose

To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination.

Methods

A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI.

Results

In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain–Barré syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma.

Conclusion

Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.

Keywords

Respiratory virus Cross-reactivity Adaptive immunity Autoimmunity Asthma 

Abbreviations

ACTH

Adrenocorticotropin

Ad

Adenoviruses

ADEM

Acute disseminated encephalomyelitis

APC

Antigen presenting cell

BRSV

Bovine RSV

CD

Celiac disease

CMV

Cytomegalovirus

COBRA

Computationally optimized broadly reactive antigen

COPD

Chronic obstructive pulmonary disease

CoV

Coronavirus

CV

Coxsackie virus

EAE

Experimental autoimmune encephalomyelitis

EBV

Epstein–Barr virus

F

Anti-fusion protein

G

Anti-attachment glycoprotein

GBS

Guillain–Barré syndrome

GM3

Monosialodihexosylganglioside

HCV

Hepatitis C virus

HCV-SN

HCV seronegative

HDM

House dust mite

HI

Heterologous immunity

HIV

Human immunodeficiency virus

HLA

Human leukocyte antigen

HMPV

Human metapneumovirus

HPV

Human papilloma viruses

IFN

Interferon

IL

Interleukin

IM

Infectious mononucleosis

IV

Influenza virus

kDa

Kilodalton

LAIV

Live attenuated influenza vaccine

LRTI

Lower respiratory tract infections

mAb

Monoclonal antibody

MBP

Myelin basic protein

MERS

Middle East respiratory syndrome

MHC

Major histocompatibility complex

MOG

Myelin oligodendrocyte protein

MYHC

Myosin heavy chain

NKT

natural killer T

NMDAR

Anti-N-methyl-D-aspartate receptor

OVA

Ovalbumin

pMHC

peptide-MHC

rRBD

Recombinant receptor binding-domain

RSV

Respiratory syncytial virus

RTI

Respiratory tract infections

RV

Rhinovirus

S

Spike

SARS

Severe acute respiratory syndrome

SLE

Systemic lupus erythematosus

SS

Sjögren’s syndrome

T1DM

Type 1 diabetes mellitus

TCR

TCR

Tem

T effector memory cells

TLR2

Toll-like receptor 2

Tm

T memory

TRIB2

Tribbles homolog 2

Trm

Tissue resident memory

URTI

Upper respiratory tract infections

VP

Viral capsid proteins

Notes

Acknowledgements

The work was supported by the German Research Foundation, SFB 1021, Project C04 and the German Center for Lung Research (DZL).

Conflict of interest

C. Skevaki has received grants from the German Research Foundation, the German Center for Lung Research, Hycor and Mead Johnson Nutritional and consultancy fees by Hycor and Bencard. H. Renz has received a grant from the German Research Foundation and the German Center for Lung Research and payment for lectures from Allergopharma, Novartis, Thermo Fisher, Danone, Mead Johnson Nutritional, and Bencard and has received payment for research and development projects from Hycor, Mead Johnson, and Beckman Coulter. E. Pusch declares no relevant conflicts of interest.

References

  1. 1.
    Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003;163:487.  https://doi.org/10.1001/archinte.163.4.487.PubMedCrossRefGoogle Scholar
  2. 2.
    Molinari N‑AM, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25:5086–96.  https://doi.org/10.1016/j.vaccine.2007.03.046.PubMedCrossRefGoogle Scholar
  3. 3.
    Mäkelä MJ, Puhakka T, Ruuskanen O, Leinonen M, Saikku P, Kimpimäki M, et al. Viruses and bacteria in the etiology of the common cold. J Clin Microbiol. 1998;36:539–42.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415–27.  https://doi.org/10.1056/NEJMoa1500245.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385:430–40.  https://doi.org/10.1016/S0140-6736(14)61698-6.PubMedCrossRefGoogle Scholar
  6. 6.
    Nair H, Brooks WA, Katz M, Roca A, Berkley JA, Madhi SA, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet. 2011;378:1917–30.  https://doi.org/10.1016/S0140-6736(11)61051-9.PubMedCrossRefGoogle Scholar
  7. 7.
    Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–55.  https://doi.org/10.1016/S0140-6736(10)60206-1.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Wedzicha JA, Seemungal TAR. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370:786–96.  https://doi.org/10.1016/S0140-6736(07)61382-8.PubMedCrossRefGoogle Scholar
  9. 9.
    Jartti T, Gern JE. Role of viral infections in the development and exacerbation of asthma in children. J Allergy Clin Immunol. 2017;140:895–906.  https://doi.org/10.1016/j.jaci.2017.08.003.PubMedCrossRefGoogle Scholar
  10. 10.
    Holt PG, Sly PD. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Nat Med. 2012;18:726–35.  https://doi.org/10.1038/nm.2768.PubMedCrossRefGoogle Scholar
  11. 11.
    Cusick MF, Libbey JE, Fujinami RS. Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol. 2012;42:102–11.  https://doi.org/10.1007/s12016-011-8294-7.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Netea MG, Quintin J, van der Meer JWM. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011;9:355–61.  https://doi.org/10.1016/j.chom.2011.04.006.PubMedCrossRefGoogle Scholar
  13. 13.
    Goodridge HS, Ahmed SS, Curtis N, Kollmann TR, Levy O, Netea MG, et al. Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol. 2016;16:392–400.  https://doi.org/10.1038/nri.2016.43.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Martin SF. Adaptation in the innate immune system and heterologous innate immunity. Cell Mol Life Sci. 2014;71:4115–30.  https://doi.org/10.1007/s00018-014-1676-2.PubMedCrossRefGoogle Scholar
  15. 15.
    Corti D, Bianchi S, Vanzetta F, Minola A, Perez L, Agatic G, et al. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature. 2013;501:439–43.  https://doi.org/10.1038/nature12442.PubMedCrossRefGoogle Scholar
  16. 16.
    D’Orsogna L, van den Heuvel H, van Kooten C, Heidt S, Claas FHJ. Infectious pathogens may trigger specific allo-HLA reactivity via multiple mechanisms. Immunogenetics. 2017;69:631–41.  https://doi.org/10.1007/s00251-017-0989-3.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Guo H, Topham DJ. Multiple distinct forms of CD8+ T cell cross-reactivity and specificities revealed after 2009 H1N1 influenza A virus infection in mice. PLoS ONE. 2012;7:1–11.  https://doi.org/10.1371/journal.pone.0046166.CrossRefGoogle Scholar
  18. 18.
    Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19:1305–12.  https://doi.org/10.1038/nm.3350.PubMedCrossRefGoogle Scholar
  19. 19.
    Steinke JW, Liu L, Turner RB, Braciale TJ, Borish L. Immune surveillance by rhinovirus-specific circulating CD4+ and CD8+ T lymphocytes. PLoS ONE. 2015;10:e115271.  https://doi.org/10.1371/journal.pone.0115271.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012;18:276–82.  https://doi.org/10.1038/nm.2612.CrossRefGoogle Scholar
  21. 21.
    Acierno PM, Newton DA, Brown EA, Maes L, Baatz JE, Gattoni-Celli S, et al. Cross-reactivity between HLA-A2-restricted FLU-M1:58–66 and HIV p17 GAG:77–85 epitopes in HIV-infected and uninfected individuals. J Transl Med. 2003;1(3)  https://doi.org/10.1186/1479-5876-1-3.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Wedemeyer H, Mizukoshi E, Davis AR, Bennink JR, Rehermann B. Cross-reactivity between hepatitis C virus and Influenza A virus determinant-specific cytotoxic T cells. J Virol. 2001;75:11392–400.  https://doi.org/10.1128/JVI.75.23.11392.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Su L, Kidd B, Han A, Kotzin J, Davis M. Virus-specific CD4+ memory-phenotype T cells are abundant in unexposed adults. Immunity. 2013;38:373–83.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Vujanovic L, Shi J, Kirkwood JM, Storkus WJ, Butterfield LH. Molecular mimicry of MAGE-A6 and mycoplasma penetrans HF-2 epitopes in the induction of antitumor CD8+ T‑cell responses. Oncoimmunology. 2014;3:e954501.  https://doi.org/10.4161/21624011.2014.954501.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Johnson LR, Weizman O‑E, Rapp M, Way SS, Sun JC. Epitope-specific vaccination limits clonal expansion of heterologous naive T cells during viral challenge. Cell Rep. 2016;17:636–44.  https://doi.org/10.1016/j.celrep.2016.09.019.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Oberle SG, Hanna-El-Daher L, Chennupati V, Enouz S, Scherer S, Prlic M, Zehn D. A minimum epitope overlap between infections strongly narrows the emerging T cell repertoire. Cell Rep. 2016;17:627–35.  https://doi.org/10.1016/j.celrep.2016.09.072.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Urbani S, Amadei B, Fisicaro P, Pilli M, Missale G, Bertoletti A, Ferrari C. Heterologous T cell immunity in severe hepatitis C virus infection. J Exp Med. 2005;201:675–80.  https://doi.org/10.1084/jem.20041058.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Welsh RM, Che JW, Brehm MA, Selin LK. Heterologous immunity between viruses. Immunol Rev. 2010;235:244–66.  https://doi.org/10.1111/j.0105-2896.2010.00897.x.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995;80:695–705.  https://doi.org/10.1016/0092-8674(95)90348-8.PubMedCrossRefGoogle Scholar
  30. 30.
    Heutinck KM, Yong SL, Tonneijck L, van den Heuvel H, van der Weerd NC, van der Pant KAMI, et al. Virus-specific CD8(+) T cells cross-reactive to donor-alloantigen are transiently present in the circulation of kidney transplant recipients infected with CMV and/or EBV. Am J Transplant. 2016;16:1480–91.  https://doi.org/10.1111/ajt.13618.PubMedCrossRefGoogle Scholar
  31. 31.
    Younes S‑A, Freeman ML, Mudd JC, Shive CL, Reynaldi A, Panigrahi S, et al. IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. J Clin Invest. 2016;126:2745–56.  https://doi.org/10.1172/JCI85996.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Lertmemongkolchai G, Cai G, Hunter CA, Bancroft GJ. Bystander activation of CD8+ T cells contributes to the rapid production of IFN- in response to bacterial pathogens. J Immunol. 2001;166:1097–105.  https://doi.org/10.4049/jimmunol.166.2.1097.PubMedCrossRefGoogle Scholar
  33. 33.
    Kohlmeier JE, Cookenham T, Roberts AD, Miller SC, Woodland DL. Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge. Immunity. 2010;33:96–105.  https://doi.org/10.1016/j.immuni.2010.06.016.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kamath AT, Sheasby CE, Tough DF. Dendritic cells and NK cells stimulate bystander T cell activation in response to TLR agonists through secretion of IFN-alpha beta and IFN-gamma. J Immunol. 2005;174:767–76.  https://doi.org/10.4049/jimmunol.174.2.767.PubMedCrossRefGoogle Scholar
  35. 35.
    Chu T, Tyznik AJ, Roepke S, Berkley AM, Woodward-Davis A, Pattacini L, et al. Bystander-activated memory CD8 T cells control early pathogen load in an innate-like, NKG2D-dependent manner. Cell Rep. 2013;3:701–8.  https://doi.org/10.1016/j.celrep.2013.02.020.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    McMaster SR, Wilson JJ, Wang H, Kohlmeier JE. Airway-resident memory CD8 T cells provide antigen-specific protection against respiratory virus challenge through rapid IFN-gamma production. J Immunol. 2015;195:203–9.  https://doi.org/10.4049/jimmunol.1402975.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, et al. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nat Commun. 2015;6:10224.  https://doi.org/10.1038/ncomms10224.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Lee Y‑N, Lee Y‑T, Kim M‑C, Gewirtz AT, Kang S‑M. A novel vaccination strategy mediating the induction of lung-resident memory CD8 T cells confers heterosubtypic immunity against future pandemic influenza virus. J Immunol. 2016;196:2637–45.  https://doi.org/10.4049/jimmunol.1501637.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Zens KD, Chen JK, Farber DL. Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection. JCI Insight. 2016;  https://doi.org/10.1172/jci.insight.85832.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Che JW, Selin LK, Welsh RM. Evaluation of non-reciprocal heterologous immunity between unrelated viruses. Virology. 2015;482:89–97.  https://doi.org/10.1016/j.virol.2015.03.002.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Sewell AK. Why must T cells be cross-reactive? Nat Rev Immunol. 2012;12:669–77.  https://doi.org/10.1038/nri3279.PubMedCrossRefGoogle Scholar
  42. 42.
    Arstila TP. A direct estimate of the human T cell receptor diversity. Science. 1999;286:958–61.  https://doi.org/10.1126/science.286.5441.958.PubMedCrossRefGoogle Scholar
  43. 43.
    Mason D. A very high level of crossreactivity is an essential feature of the T‑cell receptor. Immunol Today. 1998;19:395–404.  https://doi.org/10.1016/S0167-5699(98)01299-7.PubMedCrossRefGoogle Scholar
  44. 44.
    Wooldridge L, Ekeruche-Makinde J, van den Berg HA, Skowera A, Miles JJ, Tan MP, et al. A single autoimmune T cell receptor recognizes more than a million different peptides. J Biol Chem. 2012;287:1168–77.  https://doi.org/10.1074/jbc.M111.289488.PubMedCrossRefGoogle Scholar
  45. 45.
    Kagnoff MF, Austin RK, Hubert JJ, Bernardin JE, Kasarda DD. Possible role for a human adenovirus in the pathogenesis of celiac disease. J Exp Med. 1984;160(5):1544–57.PubMedCrossRefGoogle Scholar
  46. 46.
    Nilges K, Höhn H, Pilch H, Neukirch C, Freitag K, Talbot PJ, Maeurer MJ. Human papillomavirus type 16 E7 peptide-directed CD8+ T cells from patients with cervical cancer are cross-reactive with the coronavirus NS2 protein. J Virol. 2003;77:5464–74.  https://doi.org/10.1128/JVI.77.9.5464.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Valkenburg SA, Josephs TM, Clemens EB, Grant EJ, Nguyen THO, Wang GC, et al. Molecular basis for universal HLA-A*0201-restricted CD8+ T‑cell immunity against influenza viruses. Proc Natl Acad Sci USA. 2016;113:4440–5.  https://doi.org/10.1073/pnas.1603106113.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Clute SC, Watkin LB, Cornberg M, Naumov YN, Sullivan JL, Luzuriaga K, et al. Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. J Clin Invest. 2005;115:3602–12.  https://doi.org/10.1172/JCI25078.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Cornberg M, Clute SC, Watkin LB, Saccoccio FM, Kim S‑K, Naumov YN, et al. CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections. J Immunol. 2010;184:2825–38.  https://doi.org/10.4049/jimmunol.0902168.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Markovic-Plese S, Hemmer B, Zhao Y, Simon R, Pinilla C, Martin R. High level of cross-reactivity in influenza virus hemagglutinin-specific CD4+ T‑cell response: implications for the initiation of autoimmune response in multiple sclerosis. J Neuroimmunol. 2005;169:31–8.  https://doi.org/10.1016/j.jneuroim.2005.07.014.PubMedCrossRefGoogle Scholar
  51. 51.
    Huckelhoven AG, Etschel JK, Bergmann S, Zitzelsberger K, Mueller-Schmucker SM, Harrer EG, Harrer T. Cross-reactivity between influenza matrix- and HIV-1 P17-specific CTL-A large cohort study. J Acquir Immune Defic Syndr. 2015;69:528–35.  https://doi.org/10.1097/qai.0000000000000657.PubMedCrossRefGoogle Scholar
  52. 52.
    Ekeruche-Makinde J, Miles JJ, van den Berg HA, Skowera A, Cole DK, Dolton G, et al. Peptide length determines the outcome of TCR/peptide-MHCI engagement. Blood. 2013;121:1112–23.  https://doi.org/10.1182/blood-2012-06-437202.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Adams JJ, Narayanan S, Birnbaum ME, Sidhu SS, Blevins SJ, Gee MH, et al. Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. Nat Immunol. 2016;17:87–94.  https://doi.org/10.1038/ni.3310.PubMedCrossRefGoogle Scholar
  54. 54.
    van Regenmortel MHV. Specificity, polyspecificity, and heterospecificity of antibody-antigen recognition. J Mol Recognit. 2014;27:627–39.  https://doi.org/10.1002/jmr.2394.PubMedCrossRefGoogle Scholar
  55. 55.
    Kringelum JV, Nielsen M, Padkjær SB, Lund O. Structural analysis of B‑cell epitopes in antibody: protein complexes. Mol Immunol. 2013;53:24–34.  https://doi.org/10.1016/j.molimm.2012.06.001.PubMedCrossRefGoogle Scholar
  56. 56.
    Sela-Culang I, Kunik V, Ofran Y. The structural basis of antibody-antigen recognition. Front Immunol. 2013;4:302.  https://doi.org/10.3389/fimmu.2013.00302.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Channappanavar R, Fett C, Zhao J, Meyerholz DK, Perlman S. Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J Virol. 2014;88:11034–44.  https://doi.org/10.1128/JVI.01505-14.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, Gao GF. T‑cell immunity of SARS-coV: implications for vaccine development against MERS-coV. Antiviral Res. 2017;137:82–92.  https://doi.org/10.1016/j.antiviral.2016.11.006.PubMedCrossRefGoogle Scholar
  59. 59.
    Tai W, Wang Y, Fett CA, Zhao G, Li F, Perlman S, et al. Recombinant receptor-binding domains of multiple middle east respiratory syndrome coronaviruses (MERS-coVs) induce cross-neutralizing antibodies against divergent human and camel MERS-covs and antibody escape mutants. J Virol. 2017;  https://doi.org/10.1128/JVI.01651-16.CrossRefPubMedGoogle Scholar
  60. 60.
    Zhao J, Zhao J, Mangalam AK, Channappanavar R, Fett C, Meyerholz DK, et al. Airway memory CD4(+) T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity. 2016;44:1379–91.  https://doi.org/10.1016/j.immuni.2016.05.006.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, et al. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol. 2010;84:6527–35.  https://doi.org/10.1128/JVI.00519-10.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Li J, Arévalo MT, Chen Y, Chen S, Zeng M. T‑cell-mediated cross-strain protective immunity elicited by prime-boost vaccination with a live attenuated influenza vaccine. Int J Infect Dis. 2014;27:37–43.  https://doi.org/10.1016/j.ijid.2014.05.016.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Mohn KGI, Zhou F, Brokstad KA, Sridhar S, Cox RJ. Boosting of cross-reactive and protection-associated T cells in children after live attenuated influenza vaccination. J Infect Dis. 2017;215:1527–35.  https://doi.org/10.1093/infdis/jix165.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Magini D, Giovani C, Mangiavacchi S, Maccari S, Cecchi R, Ulmer JB, et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS ONE. 2016;11:e161193.  https://doi.org/10.1371/journal.pone.0161193.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Chua BY, Wong CY, Mifsud EJ, Edenborough KM, Sekiya T, Tan ACL, et al. Inactivated influenza vaccine that provides rapid, innate-immune- system-mediated protection and subsequent long-term adaptive immunity. MBio. 2015;6:1–11.  https://doi.org/10.1128/mBio.01024-15.CrossRefGoogle Scholar
  66. 66.
    Krammer F, Palese P. Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr Opin Virol. 2013;3:521–30.  https://doi.org/10.1016/j.coviro.2013.07.007.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Ellebedy AH, Krammer F, Li G‑M, Miller MS, Chiu C, Wrammert J, et al. Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. Proc Natl Acad Sci USA. 2014;111:13133–8.  https://doi.org/10.1073/pnas.1414070111.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Krammer F. Novel universal influenza virus vaccine approaches. Curr Opin Virol. 2016;17:95–103.  https://doi.org/10.1016/j.coviro.2016.02.002.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Carter DM, Darby CA, Lefoley BC, Crevar CJ, Alefantis T, Oomen R, et al. Design and characterization of a computationally optimized broadly reactive hemagglutinin vaccine for H1N1 influenza viruses. J Virol. 2016;90:4720–34.  https://doi.org/10.1128/JVI.03152-15.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Deng L, Cho KJ, Fiers W, Saelens X. M2e-based universal influenza A vaccines. Vaccines (Basel). 2015;3:105–36.  https://doi.org/10.3390/vaccines3010105.CrossRefGoogle Scholar
  71. 71.
    Eliasson DG, Omokanye A, Schön K, Wenzel UA, Bernasconi V, Bemark M, et al. M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection. Mucosal Immunol. 2017;  https://doi.org/10.1038/mi.2017.14.PubMedCrossRefGoogle Scholar
  72. 72.
    Schotsaert M, Ysenbaert T, Smet A, Schepens B, Vanderschaeghe D, Stegalkina S, et al. Long-lasting cross-protection against influenza A by neuraminidase and M2e-based immunization strategies. Sci Rep. 2016;  https://doi.org/10.1038/srep24402.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Ramos EL, Mitcham JL, Koller TD, Bonavia A, Usner DW, Balaratnam G, et al. Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza. J Infect Dis. 2015;211:1038–44.  https://doi.org/10.1093/infdis/jiu539.PubMedCrossRefGoogle Scholar
  74. 74.
    Graham BS. Vaccines against respiratory syncytial virus: the time has finally come. Vaccine. 2016;34:3535–41.  https://doi.org/10.1016/j.vaccine.2016.04.083.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Cortjens B, Yasuda E, Yu X, Wagner K, Claassen YB, Bakker AQ, et al. Broadly reactive anti-respiratory syncytial virus G antibodies from exposed individuals effectively inhibit infection of primary airway epithelial cells. J Virol. 2017;  https://doi.org/10.1128/JVI.02357-16.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Lee J‑Y, Chang J. Universal vaccine against respiratory syncytial virus A and B subtypes. PLoS ONE. 2017;12:e175384.  https://doi.org/10.1371/journal.pone.0175384.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Taylor G, Thom M, Capone S, Pierantoni A, Guzman E, Herbert R, et al. Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections. Sci Transl Med. 2015;7:300ra127.  https://doi.org/10.1126/scitranslmed.aac5757.PubMedCrossRefGoogle Scholar
  78. 78.
    Schuster JE, Cox RG, Hastings AK, Boyd KL, Wadia J, Chen Z, et al. A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis. 2015;211:216–25.  https://doi.org/10.1093/infdis/jiu307.PubMedCrossRefGoogle Scholar
  79. 79.
    Glanville N, Mclean GR, Guy B, Lecouturier V, Berry C, Girerd Y, et al. Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein. Plos Pathog. 2013;9:e1003669.  https://doi.org/10.1371/journal.ppat.1003669.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Muehling LM, Mai DT, Kwok WW, Heymann PW, Pomes A, Woodfolk JA. Circulating memory CD4+ T cells target conserved epitopes of rhinovirus capsid proteins and respond rapidly to experimental infection in humans. J Immunol. 2016;197:3214–24.  https://doi.org/10.4049/jimmunol.1600663.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Iwasaki J, Smith W‑A, Stone SR, Thomas WR, Hales BJ. Species-specific and cross-reactive IgG1 antibody binding to viral capsid protein 1 (VP1) antigens of human rhinovirus species A, B and C. PLoS ONE. 2013;8:e70552.  https://doi.org/10.1371/journal.pone.0070552.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Niespodziana K, Napora K, Cabauatan C, Focke-Tejkl M, Keller W, Niederberger V, et al. Misdirected antibody responses against an N‑terminal epitope on human rhinovirus VP1 as explanation for recurrent RV infections. Faseb J. 2012;26:1001–8.  https://doi.org/10.1096/fj.11-193557.PubMedCrossRefGoogle Scholar
  83. 83.
    Aslan N, Watkin LB, Gil A, Mishra R, Clark FG, Welsh RM, et al. Severity of acute infectious mononucleosis correlates with cross-reactive influenza CD8 T‑cell receptor repertoires. MBio. 2017;  https://doi.org/10.1128/mBio.01841-17.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Odumade OA, Knight JA, Schmeling DO, Masopust D, Balfour HH. Primary Epstein-Barr virus infection does not erode preexisting CD8(+) T cell memory in humans. J Exp Med. 2012;209:471–8.  https://doi.org/10.1084/jem.20112401.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Watkin LB, Mishra R, Gil A, Aslan N, Ghersi D, Luzuriaga K, Selin LK. Unique influenza A cross-reactive memory CD8 T‑cell receptor repertoire has a potential to protect against EBV seroconversion. J Allergy Clin Immunol. 2017;140:1206–10.  https://doi.org/10.1016/j.jaci.2017.05.037.PubMedCrossRefGoogle Scholar
  86. 86.
    Zhang S, Bakshi RK, Suneetha PV, Fytili P, Antunes DA, Vieira GF, et al. Frequency, private specificity, and cross-reactivity of preexisting hepatitis C virus (HCV)-specific CD8+ T cells in HCV-seronegative individuals: implications for vaccine responses. J Virol. 2015;89:8304–17.  https://doi.org/10.1128/JVI.00539-15.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Kasprowicz V, Ward SM, Turner A, Grammatikos A, Nolan BE, Lewis-ximenez L, et al. Defining the directionality and quality of influenza virus—specific CD8 + T cell cross-reactivity in individuals infected with hepatitis C virus. J Clin Invest. 2008;118:1143–53.  https://doi.org/10.1172/JCI33082DS1.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Ertl HC. Viral vectors as vaccine carriers. Curr Opin Virol. 2016;17:1–8.  https://doi.org/10.1016/j.coviro.2016.06.001.CrossRefGoogle Scholar
  89. 89.
    Kotterman MA, Chalberg TW, Schaffer DV. Viral vectors for gene therapy: translational and clinical outlook. Annu Rev Biomed Eng. 2015;17:63–89.  https://doi.org/10.1146/annurev-bioeng-071813-104938.PubMedCrossRefGoogle Scholar
  90. 90.
    Singh S, Vedi S, Samrat SK, Li W, Kumar R, Agrawal B. Heterologous immunity between adenoviruses and hepatitis C virus: a new paradigm in HCV immunity and vaccines. PLoS ONE. 2016;11:1–23.  https://doi.org/10.1371/journal.pone.0146404.CrossRefGoogle Scholar
  91. 91.
    Frahm N, DeCamp AC, Friedrich DP, Carter DK, Defawe OD, Kublin JG, et al. Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J Clin Invest. 2012;122:359–67.  https://doi.org/10.1172/JCI60202.PubMedCrossRefGoogle Scholar
  92. 92.
    Pennington SH, Thompson AL, Wright AKA, Ferreira DM, Jambo KC, Wright AD, et al. Oral typhoid vaccination with live-attenuated Salmonella typhi strain Ty21a generates Ty21a-responsive and heterologous influenza virus–responsive CD4 + and CD8 + T cells at the human intestinal mucosa. J Infect Dis. 2016;213:1809–19.  https://doi.org/10.1093/infdis/jiw030.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Tenembaum S, Chitnis T, Ness J, Hahn JS. Acute disseminated encephalomyelitis. Neurology. 2007;68(16 Suppl 2):S23–S36.PubMedCrossRefGoogle Scholar
  94. 94.
    Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. Autoimmun Rev. 2014;13:215–24.  https://doi.org/10.1016/j.autrev.2013.10.003.PubMedCrossRefGoogle Scholar
  95. 95.
    Ravaglia S, Ceroni M, Moglia A, Todeschini A, Marchioni E. Post-infectious and post-vaccinal acute disseminated encephalomyelitis occurring in the same patients. J Neurol. 2004;251:1147–50.  https://doi.org/10.1007/s00415-004-0498-9.PubMedCrossRefGoogle Scholar
  96. 96.
    Athauda D, Andrews TC, Holmes PA, Howard RS. Multiphasic acute disseminated encephalomyelitis (ADEM) following influenza type A (swine specific H1N1). J Neurol. 2012;259:775–8.  https://doi.org/10.1007/s00415-011-6258-8.PubMedCrossRefGoogle Scholar
  97. 97.
    Au WY, Lie AKW, Cheung RTF, Cheng PW, Ooi CGC, Yujenc K‑Y, Kwong Y‑L. Acute disseminated encephalomyelitis after para-influenza infection post bone marrow transplantation. Leuk Lymphoma. 2002;43:455–7.  https://doi.org/10.1080/10428190290006350.PubMedCrossRefGoogle Scholar
  98. 98.
    Sellers SA, Hagan RS, Hayden FG, Fischer WA. The hidden burden of influenza: a review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017;11:372–93.  https://doi.org/10.1111/irv.12470.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Blackmore S, Hernandez J, Juda M, Ryder E, Freund GG, Johnson RW, Steelman AJ. Influenza infection triggers disease in a genetic model of experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA. 2017;114:E6107–E16.  https://doi.org/10.1073/pnas.1620415114.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Chen Q, Liu Y, Lu A, Ni K, Xiang Z, Wen K, Tu W. Influenza virus infection exacerbates experimental autoimmune encephalomyelitis disease by promoting type I T cells infiltration into central nervous system. J Autoimmun. 2017;77:1–10.  https://doi.org/10.1016/j.jaut.2016.10.006.PubMedCrossRefGoogle Scholar
  101. 101.
    Sriram S, Steiner I. Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann Neurol. 2005;58:939–45.  https://doi.org/10.1002/ana.20743.PubMedCrossRefGoogle Scholar
  102. 102.
    Pohl-Koppe A, Burchett SK, Thiele EA, Hafler DA. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. J Neuroimmunol. 1998;91:19–27.  https://doi.org/10.1016/S0165-5728(98)00125-8.PubMedCrossRefGoogle Scholar
  103. 103.
    Hennes E‑M, Baumann M, Schanda K, Anlar B, Bajer-Kornek B, Blaschek A, et al. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology. 2017;89:900–8.  https://doi.org/10.1212/WNL.0000000000004312.PubMedCrossRefGoogle Scholar
  104. 104.
    Boucher A, Desforges M, Duquette P, Talbot PJ. Long-term human coronavirus-myelin cross-reactive T‑cell clones derived from multiple sclerosis patients. Clin Immunol. 2007;123:258–67.  https://doi.org/10.1016/j.clim.2007.02.002.PubMedCrossRefGoogle Scholar
  105. 105.
    Peschl P, Bradl M, Höftberger R, Berger T, Reindl M. Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol. 2017;8:529.  https://doi.org/10.3389/fimmu.2017.00529.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Lehmann HC, Hartung H‑P, Kieseier BC, Hughes RA. Guillain-Barré syndrome after exposure to influenza virus. Lancet Infect Dis. 2010;10:643–51.PubMedCrossRefGoogle Scholar
  107. 107.
    Martín Arias LH, Sanz R, Sáinz M, Treceño C, Carvajal A. Guillain-Barré syndrome and influenza vaccines: a meta-analysis. Vaccine. 2015;33:3773–8.  https://doi.org/10.1016/j.vaccine.2015.05.013.PubMedCrossRefGoogle Scholar
  108. 108.
    Nachamkin I, Shadomy SV, Moran AP, Cox N, Fitzgerald C, Ung H, et al. Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barré syndrome. J Infect Dis. 2008;198:226–33.  https://doi.org/10.1086/589624.PubMedCrossRefGoogle Scholar
  109. 109.
    Partinen M, Kornum BR, Plazzi G, Jennum P, Julkunen I, Vaarala O. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol. 2014;13:600–13.  https://doi.org/10.1016/S1474-4422(14)70075-4.PubMedCrossRefGoogle Scholar
  110. 110.
    Han F, Lin L, Warby SC, Faraco J, Li J, Dong SX, et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann Neurol. 2011;70:410–7.  https://doi.org/10.1002/ana.22587.PubMedCrossRefGoogle Scholar
  111. 111.
    Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med. 2015;7:294ra105.  https://doi.org/10.1126/scitranslmed.aab2354.PubMedCrossRefGoogle Scholar
  112. 112.
    Saariaho A‑H, Vuorela A, Freitag TL, Pizza F, Plazzi G, Partinen M, et al. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after pandemrix vaccination against 2009 pandemic H1N1 type influenza virus. J Autoimmun. 2015;63:68–75.  https://doi.org/10.1016/j.jaut.2015.07.006.PubMedCrossRefGoogle Scholar
  113. 113.
    Cvetkovic-Lopes V, Bayer L, Dorsaz S, Maret S, Pradervand S, Dauvilliers Y, et al. Elevated tribbles homolog 2‑specific antibody levels in narcolepsy patients. J Clin Invest. 2010;120:713–9.  https://doi.org/10.1172/JCI41366.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Lind A, Ramelius A, Olsson T, Arnheim-Dahlström L, Lamb F, Khademi M, et al. A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the pandemrix vaccination campaign in Sweden 2009–2010. J Autoimmun. 2014;50:99–106.  https://doi.org/10.1016/j.jaut.2014.01.031.PubMedCrossRefGoogle Scholar
  115. 115.
    Katzav A, Arango MT, Kivity S, Tanaka S, Givaty G, Agmon-Levin N, et al. Passive transfer of narcolepsy: anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice. J Autoimmun. 2013;45:24–30.  https://doi.org/10.1016/j.jaut.2013.06.010.PubMedCrossRefGoogle Scholar
  116. 116.
    Prüss H, Finke C, Höltje M, Hofmann J, Klingbeil C, Probst C, et al. N‑methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol. 2012;72:902–11.  https://doi.org/10.1002/ana.23689.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Berger B, Pytlik M, Hottenrott T, Stich O. Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections. Int J Neurosci. 2017;127:109–17.  https://doi.org/10.3109/00207454.2016.1147447.PubMedCrossRefGoogle Scholar
  118. 118.
    Brown AS. Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol. 2012;72:1272–6.  https://doi.org/10.1002/dneu.22024.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Lucchese G, Capone G, Kanduc D. Peptide sharing between influenza A H1N1 hemagglutinin and human axon guidance proteins. Schizophr Bull. 2014;40:362–75.  https://doi.org/10.1093/schbul/sbs197.PubMedCrossRefGoogle Scholar
  120. 120.
    Lucchese G. Understanding neuropsychiatric diseases, analyzing the peptide sharing between infectious agents and the language-associated NMDA 2A protein. Front Psychiatry. 2016;7:60.  https://doi.org/10.3389/fpsyt.2016.00060.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Wheatland R. Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression. Med Hypotheses. 2005;65:287–95.  https://doi.org/10.1016/j.mehy.2005.02.031.PubMedCrossRefGoogle Scholar
  122. 122.
    Wheatland R. Molecular mimicry of ACTH in SARS—implications for corticosteroid treatment and prophylaxis. Med Hypotheses. 2004;63:855–62.  https://doi.org/10.1016/j.mehy.2004.04.009.PubMedCrossRefGoogle Scholar
  123. 123.
    Beyerlein A, Donnachie E, Ziegler A‑G. Infections in early life and development of celiac disease. Am J Epidemiol. 2017;  https://doi.org/10.1093/aje/kwx190.PubMedCrossRefGoogle Scholar
  124. 124.
    Kagnoff MF, Paterson YJ, Kumar PJ, Kasarda DD, Carbone FR, Unsworth DJ, Austin RK. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease. Gut. 1987;28:995–1001.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Mantzaris GJ, Karagiannis JA, Priddle JD, Jewell DP. Cellular hypersensitivity to a synthetic dodecapeptide derived from human adenovirus 12 which resembles a sequence of A‑gliadin in patients with coeliac disease. Gut. 1990;31:668–73.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Kupfer SS, Jabri B. Pathophysiology of celiac disease. Gastrointest Endosc Clin N Am. 2012;22:639–60.  https://doi.org/10.1016/j.giec.2012.07.003.PubMedCrossRefGoogle Scholar
  127. 127.
    Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34:2636–2648, 2648a-2648d.  https://doi.org/10.1093/eurheartj/eht210.PubMedCrossRefGoogle Scholar
  128. 128.
    Massilamany C, Gangaplara A, Steffen D, Reddy J. Identification of novel mimicry epitopes for cardiac myosin heavy chain-α that induce autoimmune myocarditis in A/J mice. Cell Immunol. 2011;271:438–49.  https://doi.org/10.1016/j.cellimm.2011.08.013.PubMedCrossRefGoogle Scholar
  129. 129.
    Gangaplara A, Massilamany C, Brown DM, Delhon G, Pattnaik AK, Chapman N, et al. Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-α-reactive CD4 T cells in A/J mice. Clin Immunol. 2012;144:237–49.  https://doi.org/10.1016/j.clim.2012.07.003.PubMedCrossRefGoogle Scholar
  130. 130.
    Root-Bernstein R. Rethinking molecular mimicry in rheumatic heart disease and autoimmune myocarditis: laminin, collagen IV, CAR, and B1AR as initial targets of disease. Front Pediatr. 2014;2:85.  https://doi.org/10.3389/fped.2014.00085.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Igoe A, Scofield RH. Autoimmunity and infection in Sjögren’s syndrome. Curr Opin Rheumatol. 2013;25:480–7.  https://doi.org/10.1097/BOR.0b013e32836200d2.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Tong L, Koh V, Thong BY-H. Review of autoantigens in Sjögren’s syndrome: an update. J Inflamm Res. 2017;10:97–105.  https://doi.org/10.2147/JIR.S137024.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Singh N, Cohen PL. The T cell in Sjogren’s syndrome: force majeure, not spectateur. J Autoimmun. 2012;39:229–33.  https://doi.org/10.1016/j.jaut.2012.05.019.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Stathopoulou EA, Routsias JG, Stea EA, Moutsopoulos HM, Tzioufas AG. Cross-reaction between antibodies to the major epitope of Ro60 kD autoantigen and a homologous peptide of Coxsackie virus 2B protein. Clin Exp Immunol. 2005;141:148–54.  https://doi.org/10.1111/j.1365-2249.2005.02812.x.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Szymula A, Rosenthal J, Szczerba BM, Bagavant H, Fu SM, Deshmukh US. T cell epitope mimicry between Sjögren’s syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria. Clin Immunol. 2014;152:1–9.  https://doi.org/10.1016/j.clim.2014.02.004.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Lönnrot M, Lynch KF, Elding Larsson H, Lernmark Å, Rewers MJ, Törn C, et al. Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study. Diabetologia. 2017;  https://doi.org/10.1007/s00125-017-4365-5.PubMedCentralCrossRefPubMedGoogle Scholar
  137. 137.
    Op de Beeck A, Eizirik DL. Viral infections in type 1 diabetes mellitus—why the β cells? Nat Rev Endocrinol. 2016;12:263–73.  https://doi.org/10.1038/nrendo.2016.30.PubMedCentralCrossRefGoogle Scholar
  138. 138.
    Hiemstra HS, Schloot NC, van Rood JJ, Willemen SJM, Franken KLMC, de Vries RRP, et al. Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc Natl Acad Sci USA. 2001;98:3988–91.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Honeyman MC, Stone NL, Falk BA, Nepom G, Harrison LC. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol. 2010;184:2204–10.  https://doi.org/10.4049/jimmunol.0900709.PubMedCrossRefGoogle Scholar
  140. 140.
    Qi Z, Hu H, Wang Z, Wang G, Li Y, Zhao X, et al. Antibodies against H1N1 influenza virus cross-react with α‑cells of pancreatic islets. J Diabetes Investig. 2017;  https://doi.org/10.1111/jdi.12690.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Thorel F, Népote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature. 2010;464:1149–54.  https://doi.org/10.1038/nature08894.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004;59:469–78.  https://doi.org/10.1111/j.1398-9995.2004.00526.x.PubMedCrossRefGoogle Scholar
  143. 143.
    Lötvall J, Pawankar R, Wallace DV, Akdis CA, Rosenwasser LJ, Weber RW, et al. We call for iCAALL: International Collaboration in Asthma, Allergy and Immunology. World Allergy Organ J. 2012;5:39–40.  https://doi.org/10.1097/WOX.0b013e3182504245.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, et al. Viruses and bacteria in acute asthma exacerbations—a GA² LEN-DARE systematic review. Allergy. 2011;66:458–68.  https://doi.org/10.1111/j.1398-9995.2010.02505.x.PubMedCrossRefGoogle Scholar
  145. 145.
    Lukkarinen M, Koistinen A, Turunen R, Lehtinen P, Vuorinen T, Jartti T. Rhinovirus-induced first wheezing episode predicts atopic but not nonatopic asthma at school age. J Allergy Clin Immunol. 2017;140:988–95.  https://doi.org/10.1016/j.jaci.2016.12.991.PubMedCrossRefGoogle Scholar
  146. 146.
    Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178:667–72.  https://doi.org/10.1164/rccm.200802-309OC.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299:1259–60.  https://doi.org/10.1136/bmj.299.6710.1259.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Garn H, Renz H. Epidemiological and immunological evidence for the hygiene hypothesis. Immunobiology. 2007;212:441–52.  https://doi.org/10.1016/j.imbio.2007.03.006.PubMedCrossRefGoogle Scholar
  149. 149.
    Machiels B, Dourcy M, Xiao X, Javaux J, Mesnil C, Sabatel C, et al. A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes. Nat Immunol. 2017;18:1310–20.PubMedCrossRefGoogle Scholar
  150. 150.
    Chang Y‑J, Kim HY, Albacker LA, Lee HH, Baumgarth N, Akira S, et al. Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J Clin Invest. 2011;121:57–69.  https://doi.org/10.1172/JCI44845.PubMedCrossRefGoogle Scholar
  151. 151.
    Conrad ML, Ferstl R, Teich R, Brand S, Blümer N, Yildirim AO, et al. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe acinetobacter lwoffii F78. J Exp Med. 2009;206:2869–77.  https://doi.org/10.1084/jem.20090845.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Wohlleben G, Muller J, Tatsch U, Hambrecht C, Herz U, Renz H, et al. Influenza A virus infection inhibits the efficient recruitment of Th2 cells into the airways and the development of airway eosinophilia. J Immunol. 2003;170:4601–11.  https://doi.org/10.4049/jimmunol.170.9.4601.PubMedCrossRefGoogle Scholar
  153. 153.
    Skevaki C, Hudemann C, Matrosovich M, Möbs C, Paul S, Wachtendorf A, et al. Influenza-derived peptides cross-react with allergens and provide asthma protection. J Allergy Clin Immunol. 2017;  https://doi.org/10.1016/j.jaci.2017.07.056.PubMedCrossRefGoogle Scholar
  154. 154.
    Bien CG, Bauer J. Autoimmune epilepsies. Neurotherapeutics. 2014;11:311–8.  https://doi.org/10.1007/s13311-014-0264-3.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, McMillan S, et al. The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med. 2010;42:587–95.  https://doi.org/10.3109/07853890.2010.505931.PubMedCrossRefGoogle Scholar
  156. 156.
    Lerner A, Arleevskaya M, Schmiedl A, Matthias T. Microbes and viruses are bugging the gut in celiac disease. Are they friends or foes? Front Microbiol. 2017;8:1392.  https://doi.org/10.3389/fmicb.2017.01392.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, a part of Springer Nature 2018

Authors and Affiliations

  • Emanuel Pusch
    • 1
  • Harald Renz
    • 1
  • Chrysanthi Skevaki
    • 1
  1. 1.Institute of Laboratory Medicine and Pathobiochemistry, Member of the German Center for Lung Research (DZL)Philipps University MarburgMarburgGermany

Personalised recommendations