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Role of Deficits in Pathogen Recognition Receptors in Infection Susceptibility

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Management of Infections in the Immunocompromised Host

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Abstract

The interindividual variability in the development and progression of many infectious diseases raises fundamental questions about their actual pathogenesis. Clinical and epidemiological studies have reported an increasing number of both monogenic defects and common polymorphisms associated with many major infectious diseases. The study of genetic variation regulating the immune response provides important insights into the human immunobiology by pinpointing directly relevant immune molecules and pathways. Genetic studies of susceptibility to infection have typically focused on defects of antibody production, lack of T cells, phagocytes, natural killer cells, or complement, each of which can cause a classic immunodeficiency syndrome. More recently, genetic defects that impair pathogen recognition by the innate immune system and increase susceptibility to selected classes of microorganisms have also been reported. In this chapter, we discuss the contribution of host genetic variation in pattern recognition receptors to susceptibility to infectious disease. By deciphering the molecular and cellular processes that regulate human susceptibility to infection, this knowledge is predicted to lay the foundations for personalized medical interventions based on risk stratification and patient-tailored immunotherapy.

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References

  1. Alcais A, Abel L, Casanova JL. Human genetics of infectious diseases: between proof of principle and paradigm. J Clin Invest. 2009;119(9):2506–14. https://doi.org/10.1172/JCI38111.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Burgner D, Jamieson SE, Blackwell JM. Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better? Lancet Infect Dis. 2006;6(10):653–63. https://doi.org/10.1016/S1473-3099(06)70601-6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Chapman SJ, Hill AV. Human genetic susceptibility to infectious disease. Nat Rev Genet. 2012;13(3):175–88. https://doi.org/10.1038/nrg3114.

    Article  PubMed  CAS  Google Scholar 

  4. Hill AV. Aspects of genetic susceptibility to human infectious diseases. Annu Rev Genet. 2006;40:469–86. https://doi.org/10.1146/annurev.genet.40.110405.090546.

    Article  PubMed  CAS  Google Scholar 

  5. Netea MG, van der Meer JW. Immunodeficiency and genetic defects of pattern-recognition receptors. N Engl J Med. 2011;364(1):60–70. https://doi.org/10.1056/NEJMra1001976.

    Article  PubMed  CAS  Google Scholar 

  6. Netea MG, Wijmenga C, O’Neill LA. Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol. 2012;13(6):535–42. https://doi.org/10.1038/ni.2284.

    Article  PubMed  CAS  Google Scholar 

  7. van der Eijk EA, van de Vosse E, Vandenbroucke JP, van Dissel JT. Heredity versus environment in tuberculosis in twins: the 1950s United Kingdom Prophit Survey Simonds and Comstock revisited. Am J Respir Crit Care Med. 2007;176(12):1281–8. https://doi.org/10.1164/rccm.200703-435OC.

    Article  PubMed  Google Scholar 

  8. Sorensen TI, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med. 1988;318(12):727–32. https://doi.org/10.1056/NEJM198803243181202.

    Article  PubMed  CAS  Google Scholar 

  9. Gingles NA, Alexander JE, Kadioglu A, Andrew PW, Kerr A, Mitchell TJ, et al. Role of genetic resistance in invasive pneumococcal infection: identification and study of susceptibility and resistance in inbred mouse strains. Infect Immun. 2001;69(1):426–34. https://doi.org/10.1128/IAI.69.1.426-434.2001.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Allison AC. Protection afforded by sickle-cell trait against subtertian malarial infection. Br Med J. 1954;1(4857):290–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Casanova JL, Abel L. Primary immunodeficiencies: a field in its infancy. Science. 2007;317(5838):617–9. https://doi.org/10.1126/science.1142963.

    Article  PubMed  CAS  Google Scholar 

  12. Misch EA, Berrington WR, Vary JC Jr, Hawn TR. Leprosy and the human genome. Microbiol Mol Biol Rev: MMBR. 2010;74(4):589–620. https://doi.org/10.1128/MMBR.00025-10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Stein CM. Genetic epidemiology of tuberculosis susceptibility: impact of study design. PLoS Pathog. 2011;7(1):e1001189. https://doi.org/10.1371/journal.ppat.1001189.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. O’Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in toll-like receptor signalling. Nat Rev Immunol. 2007;7(5):353–64. https://doi.org/10.1038/nri2079.

    Article  PubMed  CAS  Google Scholar 

  15. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801. https://doi.org/10.1016/j.cell.2006.02.015.

    Article  PubMed  CAS  Google Scholar 

  16. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010;327(5963):291–5. https://doi.org/10.1126/science.1183021.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–83.

    Article  CAS  PubMed  Google Scholar 

  18. Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A. 1998;95(2):588–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499–511. https://doi.org/10.1038/nri1391.

    Article  PubMed  CAS  Google Scholar 

  20. Hardison SE, Brown GD. C-type lectin receptors orchestrate antifungal immunity. Nat Immunol. 2012;13(9):817–22. https://doi.org/10.1038/ni.2369.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Geijtenbeek TB, Gringhuis SI. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol. 2009;9(7):465–79.

    Article  CAS  PubMed  Google Scholar 

  22. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21(7):677–87. https://doi.org/10.1038/nm.3893.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, et al. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science. 2003;300(5625):1584–7. https://doi.org/10.1126/science.1084677.

    Article  PubMed  CAS  Google Scholar 

  24. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 2003;278(11):8869–72. https://doi.org/10.1074/jbc.C200651200.

    Article  PubMed  CAS  Google Scholar 

  25. Kell AM, Gale M Jr. RIG-I in RNA virus recognition. Virology. 2015;479-480:110–21. https://doi.org/10.1016/j.virol.2015.02.017.

    Article  PubMed  CAS  Google Scholar 

  26. Ferwerda G, Girardin SE, Kullberg BJ, Le Bourhis L, de Jong DJ, Langenberg DM, et al. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog. 2005;1(3):279–85. https://doi.org/10.1371/journal.ppat.0010034.

    Article  PubMed  CAS  Google Scholar 

  27. Netea MG, Joosten LA, van der Meer JW, Kullberg BJ, van de Veerdonk FL. Immune defence against Candida fungal infections. Nat Rev Immunol. 2015;15(10):630–42. https://doi.org/10.1038/nri3897.

    Article  PubMed  CAS  Google Scholar 

  28. Schroder NW, Schumann RR. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005;5(3):156–64. https://doi.org/10.1016/S1473-3099(05)01308-3.

    Article  PubMed  Google Scholar 

  29. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25(2):187–91. https://doi.org/10.1038/76048.

    Article  PubMed  CAS  Google Scholar 

  30. Lorenz E, Mira JP, Frees KL, Schwartz DA. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002;162(9):1028–32.

    Article  CAS  PubMed  Google Scholar 

  31. Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity. 1998;9(1):143–50.

    Article  CAS  PubMed  Google Scholar 

  32. Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science. 2003;299(5615):2076–9. https://doi.org/10.1126/science.1081902.

    Article  PubMed  CAS  Google Scholar 

  33. von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008;321(5889):691–6. https://doi.org/10.1126/science.1158298.

    Article  CAS  Google Scholar 

  34. Lin SC, Lo YC, Wu H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature. 2010;465(7300):885–90. https://doi.org/10.1038/nature09121.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Bousfiha A, Picard C, Boisson-Dupuis S, Zhang SY, Bustamante J, Puel A, et al. Primary immunodeficiencies of protective immunity to primary infections. Clin Immunol. 2010;135(2):204–9. https://doi.org/10.1016/j.clim.2010.02.001.

    Article  PubMed  CAS  Google Scholar 

  36. Ku CL, von Bernuth H, Picard C, Zhang SY, Chang HH, Yang K, et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J Exp Med. 2007;204(10):2407–22. https://doi.org/10.1084/jem.20070628.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Courtois G, Smahi A, Reichenbach J, Doffinger R, Cancrini C, Bonnet M, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest. 2003;112(7):1108–15. https://doi.org/10.1172/JCI18714.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Doffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001;27(3):277–85. https://doi.org/10.1038/85837.

    Article  PubMed  CAS  Google Scholar 

  39. Janssen R, van Wengen A, Hoeve MA, ten Dam M, van der Burg M, van Dongen J, et al. The same IkappaBalpha mutation in two related individuals leads to completely different clinical syndromes. J Exp Med. 2004;200(5):559–68. https://doi.org/10.1084/jem.20040773.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000;67(6):1555–62. https://doi.org/10.1086/316914.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007;317(5844):1522–7. https://doi.org/10.1126/science.1139522.

    Article  PubMed  CAS  Google Scholar 

  42. Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science. 2006;314(5797):308–12. https://doi.org/10.1126/science.1128346.

    Article  PubMed  CAS  Google Scholar 

  43. Sancho-Shimizu V, Perez de Diego R, Lorenzo L, Halwani R, Alangari A, Israelsson E, et al. Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J Clin Invest. 2011;121(12):4889–902. https://doi.org/10.1172/JCI59259.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Perez de Diego R, Sancho-Shimizu V, Lorenzo L, Puel A, Plancoulaine S, Picard C, et al. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity. 2010;33(3):400–11. https://doi.org/10.1016/j.immuni.2010.08.014.

    Article  PubMed  CAS  Google Scholar 

  45. Herman M, Ciancanelli M, Ou YH, Lorenzo L, Klaudel-Dreszler M, Pauwels E, et al. Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J Exp Med. 2012;209(9):1567–82. https://doi.org/10.1084/jem.20111316.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Chapgier A, Kong XF, Boisson-Dupuis S, Jouanguy E, Averbuch D, Feinberg J, et al. A partial form of recessive STAT1 deficiency in humans. J Clin Invest. 2009;119(6):1502–14. https://doi.org/10.1172/JCI37083.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet. 2003;33(3):388–91. https://doi.org/10.1038/ng1097.

    Article  PubMed  CAS  Google Scholar 

  48. Gonzalez-Navajas JM, Lee J, David M, Raz E. Immunomodulatory functions of type I interferons. Nat Rev Immunol. 2012;12(2):125–35. https://doi.org/10.1038/nri3133.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Andersen LL, Mork N, Reinert LS, Kofod-Olsen E, Narita R, Jorgensen SE, et al. Functional IRF3 deficiency in a patient with herpes simplex encephalitis. J Exp Med. 2015;212(9):1371–9. https://doi.org/10.1084/jem.20142274.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ciancanelli MJ, Huang SX, Luthra P, Garner H, Itan Y, Volpi S, et al. Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science. 2015;348(6233):448–53. https://doi.org/10.1126/science.aaa1578.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, Van der Meer JW, et al. Functional consequences of toll-like receptor 4 polymorphisms. Mol Med. 2008;14(5–6):346–52. https://doi.org/10.2119/2007-00135.Ferwerda.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Ferwerda B, McCall MB, Alonso S, Giamarellos-Bourboulis EJ, Mouktaroudi M, Izagirre N, et al. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci U S A. 2007;104(42):16645–50. https://doi.org/10.1073/pnas.0704828104.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Papadopoulos AI, Ferwerda B, Antoniadou A, Sakka V, Galani L, Kavatha D, et al. Association of toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms with increased infection risk in patients with advanced HIV-1 infection. Clin Infect Dis. 2010;51(2):242–7. https://doi.org/10.1086/653607.

    Article  PubMed  CAS  Google Scholar 

  54. Schnetzke U, Spies-Weisshart B, Yomade O, Fischer M, Rachow T, Schrenk K, et al. Polymorphisms of toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia. Genes Immun. 2015;16(1):83–8. https://doi.org/10.1038/gene.2014.67.

    Article  PubMed  CAS  Google Scholar 

  55. Bochud PY, Chien JW, Marr KA, Leisenring WM, Upton A, Janer M, et al. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med. 2008;359(17):1766–77. https://doi.org/10.1056/NEJMoa0802629.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. de Boer MG, Jolink H, Halkes CJ, van der Heiden PL, Kremer D, Falkenburg JH, et al. Influence of polymorphisms in innate immunity genes on susceptibility to invasive aspergillosis after stem cell transplantation. PLoS One. 2011;6(4):e18403. https://doi.org/10.1371/journal.pone.0018403.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Koldehoff M, Beelen DW, Elmaagacli AH. Increased susceptibility for aspergillosis and post-transplant immune deficiency in patients with gene variants of TLR4 after stem cell transplantation. Transplant Infect Dis (An Official Journal of the Transplantation Society). 2013;15(5):533–9. https://doi.org/10.1111/tid.12115.

    Article  CAS  Google Scholar 

  58. Carvalho A, Pasqualotto AC, Pitzurra L, Romani L, Denning DW, Rodrigues F. Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis. 2008;197(4):618–21. https://doi.org/10.1086/526500.

    Article  PubMed  CAS  Google Scholar 

  59. Carvalho A, Cunha C, Carotti A, Aloisi T, Guarrera O, Di Ianni M, et al. Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation. Exp Hematol. 2009;37(9):1022–9. https://doi.org/10.1016/j.exphem.2009.06.004.

    Article  PubMed  CAS  Google Scholar 

  60. Wurfel MM, Gordon AC, Holden TD, Radella F, Strout J, Kajikawa O, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med. 2008;178(7):710–20. https://doi.org/10.1164/rccm.200803-462OC.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Plantinga TS, Johnson MD, Scott WK, van de Vosse E, Velez Edwards DR, Smith PB, et al. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis. 2012;205(6):934–43. https://doi.org/10.1093/infdis/jir867.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Hawn TR, Misch EA, Dunstan SJ, Thwaites GE, Lan NT, Quy HT, et al. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur J Immunol. 2007;37(8):2280–9. https://doi.org/10.1002/eji.200737034.

    Article  PubMed  CAS  Google Scholar 

  63. Carvalho A, De Luca A, Bozza S, Cunha C, D’Angelo C, Moretti S, et al. TLR3 essentially promotes protective class I-restricted memory CD8(+) T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients. Blood. 2012;119(4):967–77. https://doi.org/10.1182/blood-2011-06-362582.

    Article  PubMed  CAS  Google Scholar 

  64. Potenza L, Vallerini D, Barozzi P, Riva G, Forghieri F, Beauvais A, et al. Characterization of specific immune responses to different Aspergillus antigens during the course of invasive Aspergillosis in hematologic patients. PLoS One. 2013;8(9):e74326. https://doi.org/10.1371/journal.pone.0074326.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Cunha C, Goncalves SM, Duarte-Oliveira C, Leite L, Lagrou K, Marques A, et al. IL-10 overexpression predisposes to invasive aspergillosis by suppressing antifungal immunity. J Allergy Clin Immunol. 2017;140(3):867–870.e9. https://doi.org/10.1016/j.jaci.2017.02.034.

    Article  CAS  PubMed  Google Scholar 

  66. Hawn TR, Dunstan SJ, Thwaites GE, Simmons CP, Thuong NT, Lan NT, et al. A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. J Infect Dis. 2006;194(8):1127–34. https://doi.org/10.1086/507907.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Khor CC, Chapman SJ, Vannberg FO, Dunne A, Murphy C, Ling EY, et al. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat Genet. 2007;39(4):523–8. https://doi.org/10.1038/ng1976.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Ferwerda B, Alonso S, Banahan K, McCall MB, Giamarellos-Bourboulis EJ, Ramakers BP, et al. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Proc Natl Acad Sci U S A. 2009;106(25):10272–7. https://doi.org/10.1073/pnas.0811273106.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Miao R, Li J, Sun Z, Xu F, Shen H. Meta-analysis on the association of TIRAP S180L variant and tuberculosis susceptibility. Tuberculosis. 2011;91(3):268–72. https://doi.org/10.1016/j.tube.2011.01.006.

    Article  PubMed  Google Scholar 

  70. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410(6832):1099–103. https://doi.org/10.1038/35074106.

    Article  PubMed  CAS  Google Scholar 

  71. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, et al. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med. 2003;198(10):1563–72. https://doi.org/10.1084/jem.20031220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Grube M, Loeffler J, Mezger M, Kruger B, Echtenacher B, Hoffmann P, et al. TLR5 stop codon polymorphism is associated with invasive aspergillosis after allogeneic stem cell transplantation. Med Mycol. 2013;51(8):818–25. https://doi.org/10.3109/13693786.2013.809630.

    Article  PubMed  CAS  Google Scholar 

  73. Wlasiuk G, Khan S, Switzer WM, Nachman MW. A history of recurrent positive selection at the toll-like receptor 5 in primates. Mol Biol Evol. 2009;26(4):937–49. https://doi.org/10.1093/molbev/msp018.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Yadav M, Schorey JS. The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood. 2006;108(9):3168–75. https://doi.org/10.1182/blood-2006-05-024406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Ferwerda B, Ferwerda G, Plantinga TS, Willment JA, van Spriel AB, Venselaar H, et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med. 2009;361(18):1760–7. https://doi.org/10.1056/NEJMoa0901053.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 2010;207(2):291–7. https://doi.org/10.1084/jem.20091983.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Chai LY, de Boer MG, van der Velden WJ, Plantinga TS, van Spriel AB, Jacobs C, et al. The Y238X stop codon polymorphism in the human beta-glucan receptor dectin-1 and susceptibility to invasive aspergillosis. J Infect Dis. 2011;203(5):736–43. https://doi.org/10.1093/infdis/jiq102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Cunha C, Di Ianni M, Bozza S, Giovannini G, Zagarella S, Zelante T, et al. Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient- and donor-dependent mechanisms of antifungal immunity. Blood. 2010;116(24):5394–402. https://doi.org/10.1182/blood-2010-04-279307.

    Article  PubMed  CAS  Google Scholar 

  79. Plantinga TS, van der Velden WJ, Ferwerda B, van Spriel AB, Adema G, Feuth T, et al. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009;49(5):724–32. https://doi.org/10.1086/604714.

    Article  PubMed  CAS  Google Scholar 

  80. Wilson GJ, Marakalala MJ, Hoving JC, van Laarhoven A, Drummond RA, Kerscher B, et al. The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity. Cell Host Microbe. 2015;17(2):252–9. https://doi.org/10.1016/j.chom.2015.01.004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Glocker EO, Hennigs A, Nabavi M, Schaffer AA, Woellner C, Salzer U, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med. 2009;361(18):1727–35. https://doi.org/10.1056/NEJMoa0810719.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Lanternier F, Pathan S, Vincent QB, Liu L, Cypowyj S, Prando C, et al. Deep dermatophytosis and inherited CARD9 deficiency. N Engl J Med. 2013;369(18):1704–14. https://doi.org/10.1056/NEJMoa1208487.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Torres JM, Martinez-Barricarte R, Garcia-Gomez S, Mazariegos MS, Itan Y, Boisson B, et al. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. J Clin Invest. 2014;124(12):5239–48. https://doi.org/10.1172/JCI77493.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Bugarcic A, Hitchens K, Beckhouse AG, Wells CA, Ashman RB, Blanchard H. Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans. Glycobiology. 2008;18(9):679–85. https://doi.org/10.1093/glycob/cwn046.

    Article  PubMed  CAS  Google Scholar 

  85. Sato K, Yang XL, Yudate T, Chung JS, Wu J, Luby-Phelps K, et al. Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. J Biol Chem. 2006;281(50):38854–66. https://doi.org/10.1074/jbc.M606542200.

    Article  PubMed  CAS  Google Scholar 

  86. Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol. 2008;9(10):1179–88. https://doi.org/10.1038/ni.1651.

    Article  PubMed  CAS  Google Scholar 

  87. Foo SS, Reading PC, Jaillon S, Mantovani A, Mahalingam S. Pentraxins and Collectins: friend or foe during pathogen invasion? Trends Microbiol. 2015;23(12):799–811. https://doi.org/10.1016/j.tim.2015.09.006.

    Article  PubMed  CAS  Google Scholar 

  88. Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis. 2003;37(11):1496–505. https://doi.org/10.1086/379324.

    Article  PubMed  CAS  Google Scholar 

  89. Sprong T, van Deuren M. Mannose-binding lectin: ancient molecule, interesting future. Clin Infect Dis. 2008;47(4):517–8. https://doi.org/10.1086/590007.

    Article  PubMed  Google Scholar 

  90. Lambourne J, Agranoff D, Herbrecht R, Troke PF, Buchbinder A, Willis F, et al. Association of mannose-binding lectin deficiency with acute invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2009;49(10):1486–91. https://doi.org/10.1086/644619.

    Article  PubMed  CAS  Google Scholar 

  91. Jaillon S, Moalli F, Ragnarsdottir B, Bonavita E, Puthia M, Riva F, et al. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity. 2014;40(4):621–32. https://doi.org/10.1016/j.immuni.2014.02.015.

    Article  PubMed  CAS  Google Scholar 

  92. Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, et al. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N Engl J Med. 2014;370(5):421–32. https://doi.org/10.1056/NEJMoa1211161.

    Article  PubMed  CAS  Google Scholar 

  93. Wojtowicz A, Lecompte TD, Bibert S, Manuel O, Rueger S, Berger C, et al. PTX3 polymorphisms and invasive mold infections after solid organ transplant. Clin Infect Dis. 2015;61(4):619–22. https://doi.org/10.1093/cid/civ386.

    Article  PubMed  Google Scholar 

  94. Cunha C, Monteiro AA, Oliveira-Coelho A, Kuhne J, Rodrigues F, Sasaki SD, et al. PTX3-based genetic testing for risk of aspergillosis after lung transplant. Clin Infect Dis. 2015;61(12):1893–4. https://doi.org/10.1093/cid/civ679.

    Article  PubMed  Google Scholar 

  95. Mauri T, Coppadoro A, Bombino M, Bellani G, Zambelli V, Fornari C, et al. Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study. Crit Care. 2014;18(5):562. https://doi.org/10.1186/s13054-014-0562-5.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Carvalho A, Cunha C, Bistoni F, Romani L. Immunotherapy of aspergillosis. Clin Microbiol Infect (The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases). 2012;18(2):120–5. https://doi.org/10.1111/j.1469-0691.2011.03681.x.

    Article  CAS  Google Scholar 

  97. Zaas AK, Liao G, Chien JW, Weinberg C, Shore D, Giles SS, et al. Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genet. 2008;4(6):e1000101. https://doi.org/10.1371/journal.pgen.1000101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Notarangelo LD, Badolato R. Leukocyte trafficking in primary immunodeficiencies. J Leukoc Biol. 2009;85(3):335–43. https://doi.org/10.1189/jlb.0808474.

    Article  PubMed  CAS  Google Scholar 

  99. Lo Giudice P, Campo S, De Santis R, Salvatori G. Effect of PTX3 and voriconazole combination in a rat model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2012;56(12):6400–2. https://doi.org/10.1128/AAC.01000-12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Marra E, Sousa VL, Gaziano R, Pacello ML, Arseni B, Aurisicchio L, et al. Efficacy of PTX3 and posaconazole combination in a rat model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2014;58(10):6284–6. https://doi.org/10.1128/AAC.03038-14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Oliveira-Coelho A, Rodrigues F, Campos A Jr, Lacerda JF, Carvalho A, Cunha C. Paving the way for predictive diagnostics and personalized treatment of invasive aspergillosis. Front Microbiol. 2015;6:411. https://doi.org/10.3389/fmicb.2015.00411.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Kumar V, Cheng SC, Johnson MD, Smeekens SP, Wojtowicz A, Giamarellos-Bourboulis E, et al. Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia. Nat Commun. 2014;5:4675. https://doi.org/10.1038/ncomms5675.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, et al. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun. 2013;4:1342. https://doi.org/10.1038/ncomms2343.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Fairfax BP, Knight JC. Genetics of gene expression in immunity to infection. Curr Opin Immunol. 2014;30C:63–71. https://doi.org/10.1016/j.coi.2014.07.001.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C.C.)

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Authors and Affiliations

  1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Cristina Cunha, Samuel M. Gonçalves & Agostinho Carvalho

  2. ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Cristina Cunha, Samuel M. Gonçalves & Agostinho Carvalho

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  1. Cristina Cunha
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  2. Samuel M. Gonçalves
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  3. Agostinho Carvalho
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Correspondence to Agostinho Carvalho .

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  1. Departments of Medicine and Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA

    Brahm H. Segal

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Cunha, C., Gonçalves, S.M., Carvalho, A. (2018). Role of Deficits in Pathogen Recognition Receptors in Infection Susceptibility. In: Segal, B. (eds) Management of Infections in the Immunocompromised Host. Springer, Cham. https://doi.org/10.1007/978-3-319-77674-3_6

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