Microbial Triggers in Autoimmunity, Severe Allergy, and Autoallergy

  • Fariza M. S. Badloe
  • Sherief R. Janmohamed
  • Johannes Ring
  • Jan GutermuthEmail author
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)


The prevalence of immune-mediated diseases (allergies, autoimmune diseases, and autoinflammatory diseases) is rising world-wide and their management is difficult, since treatments usually are mainly symptomatic. Insight in the exact pathomechanisms is crucial for focused prevention or improvement of therapies.

Microbial factors including bacteria (mainly Staphylococcus aureus), viruses and fungi are important factors in atopic dermatitis. Allergic asthma is also heavily impacted by Staphylococcus aureus, but also by multiple viruses. Viral complications in severe allergies can lead to life-threatening disease states. In autoimmunity, many viruses and bacteria play a role in disease development due to molecular mimicry or bystander activation.

Furthermore, it is hypothesized that autoallergy can link allergy, chronification of disease, and autoimmunity. Here, fungal triggers are suspected to elicit autoreactive IgE and T helper 1 responses in atopic dermatitis, which can maintain a vicious inflammatory cycle due to constant autoallergen release by scratching. Taken together, multiple microbial factors elicit or aggravate immune mediated diseases, such as allergies and autoimmunity.


Allergy Asthma Atopic dermatitis Autoallergy Autoimmune diseases Microbial triggers 



Nascent polypeptide-associated complex subunit alpha


Atopic dermatitis


Antigen presenting cell

C. jejuni

Campylobacter jejuni


Coxsackievirus B4


Epstein-Barr virus


Guillain-Barré syndrome






Human leucocyte antigen

H. pylori

Helicobacter pylori


Human rhinovirus


Herpetic stromal keratitis


Influenza virus








Malassezia globosa


Major histocompatibility complex


Manganese superoxide dismutase


Methicillin-resistant Staphylococcus aureus

NK cells

Natural killer cells


Respiratory syncytial virus

S. aureus

Staphylococcus aureus

S. epidermis

Staphylococcus epidermidis


Staphylococcal enterotoxin


Type-1 diabetes


T helper cell


Toll-like receptor


Thymic stromal lymphopoietin


Conflicts of Interest


Funding Sources



  1. Baker BS (2006) The role of microorganisms in atopic dermatitis. Clin Exp Immunol 144(1):1–9. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Balaji H, Heratizadeh A, Wichmann K, Niebuhr M, Crameri R, Scheynius A, Werfel T (2011) Malassezia sympodialis thioredoxin-specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis. J Allergy Clin Immunol 128(1):92–99.e94. CrossRefPubMedGoogle Scholar
  3. Beale J, Jayaraman A, Jackson DJ, Macintyre JD, Edwards MR, Walton RP, Zhu J, Ching YM, Shamji B, Edwards M, Westwick J, Cousins DJ, Hwang YY, McKenzie A, Johnston SL, Bartlett NW (2014) Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation. Sci Trans Med 6(256):256ra134. CrossRefGoogle Scholar
  4. Bieber T (2008) Atopic dermatitis. N Engl J Med 358(14):1483–1494. CrossRefPubMedGoogle Scholar
  5. Bieber T, D’Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schappi G, Schmid-Grendelmeier P (2017) Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol 139(4s):S58–s64. CrossRefPubMedGoogle Scholar
  6. Breuer K, HA S, Kapp A, Werfel T (2002) Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol 147(1):55–61CrossRefPubMedGoogle Scholar
  7. Busse WW, Lemanske RF Jr, Gern JE (2010) Role of viral respiratory infections in asthma and asthma exacerbations. Lancet 376(9743):826–834. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chaker AM, Zissler UM, Wagenmann M, Schmidt-Weber C (2017) Biomarkers in allergic airway disease: simply complex. ORL J Oto-rhino-laryngol Relat Spec 79(1–2):72–77. CrossRefGoogle Scholar
  9. Crameri R, Faith A, Hemmann S, Jaussi R, Ismail C, Menz G, Blaser K (1996) Humoral and cell-mediated autoimmunity in allergy to Aspergillus fumigatus. J Exp Med 184(1):265–270CrossRefPubMedGoogle Scholar
  10. D’Elios MM, Bergman MP, Amedei A, Appelmelk BJ, Del Prete G (2004) Helicobacter pylori and gastric autoimmunity. Microbes Infect 6(15):1395–1401. CrossRefPubMedGoogle Scholar
  11. Deo SS, Mistry KJ, Kakade AM, Niphadkar PV (2010) Role played by Th2 type cytokines in IgE mediated allergy and asthma. Lung India 27(2):66–71. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Earl CS, An SQ, Ryan RP (2015) The changing face of asthma and its relation with microbes. Trends Microbiol 23(7):408–418. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB (2007) Epidemiology of autoimmune diseases in Denmark. J Autoimmun 29(1):1–9CrossRefPubMedPubMedCentralGoogle Scholar
  14. Endo Y, Shirai T, Saigusa M, Mochizuki E (2017) Severe acute asthma caused by Chlamydophila pneumoniae infection. Respirol Case Rep 5(4):e00239. PubMedPubMedCentralGoogle Scholar
  15. Ercolini AM, Miller SD (2009) The role of infections in autoimmune disease. Clin Exp Immunol 155(1):1–15. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Feder HM Jr, Bennett N, Modlin JF (2014) Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by Coxsackie virus A6. Lancet Infect Dis 14(1):83–86. CrossRefPubMedGoogle Scholar
  17. Glatz M, Bosshard PP, Hoetzenecker W, Schmid-Grendelmeier P (2015) The role of Malassezia spp. in atopic dermatitis. J Clin Med 4(6):1217–1228. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V, Lau L, Carroll MP, Bruce KD, Howarth PH (2014) Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS one 9(6):e100645. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Guilbert TW, Denlinger LC (2010) Role of infection in the development and exacerbation of asthma. Expert Rev Respir Med 4(1):71–83. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Hasni SA (2012) Role of Helicobacter pylori infection in autoimmune diseases. Curr Opin Rheumatol 24(4):429–434. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hiragun T, Ishii K, Hiragun M, Suzuki H, Kan T, Mihara S, Yanase Y, Bartels J, Schroder JM, Hide M (2013) Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients. J Allergy Clin Immunol 132(3):608–615.e604. CrossRefPubMedGoogle Scholar
  22. Hiragun M, Hiragun T, Ishii K, Suzuki H, Tanaka A, Yanase Y, Mihara S, Haruta Y, Kohno N, Hide M (2014) Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and cholinergic urticaria. Allergol Int 63(1):83–93. CrossRefPubMedGoogle Scholar
  23. Hong SJ (2012) The role of Mycoplasma pneumoniae infection in asthma. Allergy, Asthma Immunol Res 4(2):59–61. CrossRefGoogle Scholar
  24. Hradetzky S, Werfel T, Rosner LM (2015) Autoallergy in atopic dermatitis. Allergo J Int 24(1):16–22. CrossRefPubMedPubMedCentralGoogle Scholar
  25. Huang YJ, Marsland BJ, Bunyavanich S, O'Mahony L, Leung DY, Muraro A, Fleisher TA (2017) The microbiome in allergic disease: current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. J Allergy Clin Immunol 139(4):1099–1110. CrossRefPubMedGoogle Scholar
  26. Iikura M, Hojo M, Koketsu R, Watanabe S, Sato A, Chino H, Ro S, Masaki H, Hirashima J, Ishii S, Naka G, Takasaki J, Izumi S, Kobayashi N, Yamaguchi S, Nakae S, Sugiyama H (2015) The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice. PLoS one 10(4):e0123584. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Iramain R, De Jesus R, Spitters C, Jara A, Jimenez J, Bogado N, Cardozo L (2016) Chlamydia pneumoniae, and mycoplasma pneumoniae: are they related to severe asthma in childhood? J Asthma 53(6):618–621. CrossRefPubMedGoogle Scholar
  28. Jun SH, Lee JH, Kim SI, Choi CW, Park TI, Jung HR, Cho JW, Kim SH, Lee JC (2017) Staphylococcus aureus-derived membrane vesicles exacerbate skin inflammation in atopic dermatitis. Clin Exp Allergy 47(1):85–96. CrossRefPubMedGoogle Scholar
  29. Kaesler S, Volz T, Skabytska Y, Koberle M, Hein U, Chen KM, Guenova E, Wolbing F, Rocken M, Biedermann T (2014) Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10. J Allergy Clin Immunol 134(1):92–99. CrossRefPubMedGoogle Scholar
  30. Koczulla AR, Vogelmeier CF, Garn H, Renz H (2017) New concepts in asthma: clinical phenotypes and pathophysiological mechanisms. Drug Discov Today 22(2):388–396. CrossRefPubMedGoogle Scholar
  31. Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, Nomicos E, Polley EC, Komarow HD, Murray PR, Turner ML, Segre JA (2012) Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 22(5):850–859. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Lan F, Zhang N, Gevaert E, Zhang L, Bachert C (2016) Viruses and bacteria in Th2-biased allergic airway disease. Allergy 71(10):1381–1392. CrossRefPubMedGoogle Scholar
  33. Lieberman D, Lieberman D, Printz S, Ben-Yaakov M, Lazarovich Z, Ohana B, Friedman MG, Dvoskin B, Leinonen M, Boldur I (2003) Atypical pathogen infection in adults with acute exacerbation of bronchial asthma. Am J Respir Crit Care Med 167(3):406–410. CrossRefPubMedGoogle Scholar
  34. Lin YT, Wang CT, Chiang BL (2007) Role of bacterial pathogens in atopic dermatitis. Clin Rev Allergy Immunol 33(3):167–177. CrossRefPubMedGoogle Scholar
  35. Mathes EF, Oza V, Frieden IJ, Cordoro KM, Yagi S, Howard R, Kristal L, Ginocchio CC, Schaffer J, Maguiness S, Bayliss S, Lara-Corrales I, Garcia-Romero MT, Kelly D, Salas M, Oberste MS, Nix WA, Glaser C, Antaya R (2013) “Eczema coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics 132(1):e149–e157. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Mittermann I, Reininger R, Zimmermann M, Gangl K, Reisinger J, Aichberger KJ, Greisenegger EK, Niederberger V, Seipelt J, Bohle B, Kopp T, Akdis CA, Spitzauer S, Valent P, Valenta R (2008) The IgE-reactive autoantigen Hom s 2 induces damage of respiratory epithelial cells and keratinocytes via induction of IFN-gamma. J Investig Dermatol 128(6):1451–1459. CrossRefPubMedGoogle Scholar
  37. Mori M, Kuwabara S, Miyake M, Noda M, Kuroki H, Kanno H, Ogawara K, Hattori T (2000) Haemophilus influenzae infection and Guillain-Barre syndrome. Brain 123(Pt 10):2171–2178CrossRefPubMedGoogle Scholar
  38. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinchieri G, Segre JA, Belkaid Y (2012) Compartmentalized control of skin immunity by resident commensals. Science 337(6098):1115–1119. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Natter S, Seiberler S, Hufnagl P, Binder BR, Hirschl AM, Ring J, Abeck D, Schmidt T, Valent P, Valenta R (1998) Isolation of cDNA clones coding for IgE autoantigens with serum IgE from atopic dermatitis patients. FASEB J 12(14):1559–1569CrossRefPubMedGoogle Scholar
  40. Navarrete-Dechent C, Perez-Mateluna G, Silva-Valenzuela S, Vera-Kellet C, Borzutzky A (2016) Humoral and cellular autoreactivity to epidermal proteins in atopic dermatitis. Arch Immunol Ther Exp 64(6):435–442. CrossRefGoogle Scholar
  41. Ong PY (2014) New insights in the pathogenesis of atopic dermatitis. Pediatr Res 75(1-2):171–175. CrossRefPubMedGoogle Scholar
  42. Ong PY, Leung DY (2016) Bacterial and viral infections in atopic dermatitis: a comprehensive review. Clin Rev Allergy Immunol 51(3):329–337. CrossRefPubMedGoogle Scholar
  43. Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia-Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska-Polak A, Lodrup-Carlsen K, Makela M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic-Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T (2011) Viruses and bacteria in acute asthma exacerbations—a GA(2) LEN-DARE systematic review. Allergy 66(4):458–468. CrossRefPubMedGoogle Scholar
  44. Park HY, Kim CR, Huh IS, Jung MY, Seo EY, Park JH, Lee DY, Yang JM (2013) Staphylococcus aureus colonization in acute and chronic skin lesions of patients with atopic dermatitis. Ann Dermatol 25(4):410–416. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Park KD, Pak SC, Park KK (2016) The pathogenetic effect of natural and bacterial toxins on atopic dermatitis. Toxins 9(1):3. CrossRefPubMedCentralGoogle Scholar
  46. Pelaia G, Vatrella A, Gallelli L, Renda T, Cazzola M, Maselli R, Marsico SA (2006) Respiratory infections and asthma. Respir Med 100(5):775–784. CrossRefPubMedGoogle Scholar
  47. Ring J (1985) 1st description of an “atopic family anamnesis” in the Julio-Claudian imperial house: Augustus, Claudius, Britannicus. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 36(8):470–471Google Scholar
  48. Ring J (2016) Atopic dermatitis – eczema. Springer, Cham. Google Scholar
  49. Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, Gieler U, Lipozencic J, Luger T, Oranje AP, Schafer T, Schwennesen T, Seidenari S, Simon D, Stander S, Stingl G, Szalai S, Szepietowski JC, Taieb A, Werfel T, Wollenberg A, Darsow U (2012) Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol 26(8):1045–1060. CrossRefPubMedGoogle Scholar
  50. Schmid-Grendelmeier P, Fluckiger S, Disch R, Trautmann A, Wuthrich B, Blaser K, Scheynius A, Crameri R (2005) IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol 115(5):1068–1075. CrossRefPubMedGoogle Scholar
  51. Smyk DS, Koutsoumpas AL, Mytilinaiou MG, Rigopoulou EI, Sakkas LI, Bogdanos DP (2014) Helicobacter pylori and autoimmune disease: cause or bystander. World J Gastroenterol 20(3):613–629. CrossRefPubMedPubMedCentralGoogle Scholar
  52. Tauber M, Balica S, Hsu CY, Jean-Decoster C, Lauze C, Redoules D, Viode C, Schmitt AM, Serre G, Simon M, Paul CF (2016) Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis. J Allergy Clin Immunol 137(4):1272–1274.e1271-1273. CrossRefPubMedGoogle Scholar
  53. Thomsen SF (2015) Epidemiology and natural history of atopic diseases. Eur Clin Respir J 2:24642. CrossRefGoogle Scholar
  54. Valenta R, Natter S, Seiberler S, Wichlas S, Maurer D, Hess M, Pavelka M, Grote M, Ferreira F, Szepfalusi Z, Valent P, Stingl G (1998) Molecular characterization of an autoallergen, Hom s 1, identified by serum IgE from atopic dermatitis patients. J Investig Dermatol 111(6):1178–1183. CrossRefPubMedGoogle Scholar
  55. Vojdani A (2014) A potential link between environmental triggers and autoimmunity. Autoimmune Dis 2014:437231. PubMedPubMedCentralGoogle Scholar
  56. Wahn U (2014) K.C. Bergmann, J. Ring (Ed.): History of allergy. Pediatr Allergy Immunol 25(6):i–i. CrossRefGoogle Scholar
  57. Wallach D, Taieb A (2014) Atopic dermatitis/atopic eczema. Chem Immunol Allergy 100:81–96. CrossRefPubMedGoogle Scholar
  58. Werfel T, Heratizadeh A, Niebuhr M, Kapp A, Roesner LM, Karch A, Erpenbeck VJ, Losche C, Jung T, Krug N, Badorrek P, Hohlfeld JM (2015) Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber. J Allergy Clin Immunol 136(1):96–103.e109. CrossRefPubMedGoogle Scholar
  59. Wickham S, Carr DJ (2004) Molecular mimicry versus bystander activation: herpetic stromal keratitis. Autoimmunity 37(5):393–397. CrossRefPubMedGoogle Scholar
  60. Wollenberg A (2012) Eczema herpeticum. Chem Immunol Allergy 96:89–95. CrossRefPubMedGoogle Scholar
  61. Wollina U (2017) Microbiome in atopic dermatitis. Clin Cosmet Investig Dermatol 10:51–56. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Zissler UM, Esser-von Bieren J, Jakwerth CA, Chaker AM, Schmidt-Weber CB (2016) Current and future biomarkers in allergic asthma. Allergy 71(4):475–494. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Fariza M. S. Badloe
    • 1
  • Sherief R. Janmohamed
    • 1
  • Johannes Ring
    • 1
    • 2
  • Jan Gutermuth
    • 1
    Email author
  1. 1.Department of DermatologyVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZB)BrusselsBelgium
  2. 2.Department of Dermatology and Allergy, BiedersteinTechnical UniversityMunichGermany

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