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The Role of Interleukin-1 Family Members in the Host Defence Against Aspergillus fumigatus

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Abstract

The interleukin (IL)-1 family consists of 11 members, which all play significant roles in regulating inflammatory responses in the host. IL-1α and IL-1β exert potent pro-inflammatory effects and are key players in the recruitment of neutrophils to the site of inflammation. Protective anti-Aspergillus host responses during the early stages of invasive aspergillosis are critically dependent on neutrophil recruitment, and several lines of evidence support that there is an important role for IL-1 in this process. However, IL-1-mediated inflammation needs to be tightly regulated, since uncontrolled inflammation can result in inflammatory pathology and thereby be detrimental for the host. Aspergillus-induced IL-1-mediated inflammation could therefore be amendable for IL-1 blockade under specific circumstances. This review describes the current understanding of the role of IL-1 family members in the host response against Aspergillus fumigatus and highlights the importance of balanced IL-1 responses in aspergillosis.

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References

  1. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010;10(2):89–102. doi:10.1038/nri2691.

    Article  CAS  PubMed  Google Scholar 

  2. Suwara MI, Green NJ, Borthwick LA, Mann J, Mayer-Barber KD, Barron L, et al. IL-1alpha released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts. Mucosal Immunol. 2014;7(3):684–93. doi:10.1038/mi.2013.87.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Loeffler J, Haddad Z, Bonin M, Romeike N, Mezger M, Schumacher U, et al. Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus. J Med Microbiol. 2009;58(Pt 1):49–58. doi:10.1099/jmm.0.003293-0.

    Article  PubMed  Google Scholar 

  4. Said-Sadier N, Padilla E, Langsley G, Ojcius DM. Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS ONE. 2010;5(4):e10008. doi:10.1371/journal.pone.0010008.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Sun H, Xu XY, Tian XL, Shao HT, Wu XD, Wang Q, et al. Activation of NF-kappaB and respiratory burst following Aspergillus fumigatus stimulation of macrophages. Immunobiology. 2014;219(1):25–36. doi:10.1016/j.imbio.2013.06.013.

    Article  CAS  PubMed  Google Scholar 

  6. Latz E. The inflammasomes: mechanisms of activation and function. Curr Opin Immunol. 2010;22(1):28–33. doi:10.1016/j.coi.2009.12.004.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Gresnigt MS, Netea MG, van de Veerdonk FL. Pattern recognition receptors and their role in invasive aspergillosis. Ann N Y Acad Sci. 2012;1273:60–7. doi:10.1111/j.1749-6632.2012.06759.x.

    Article  CAS  PubMed  Google Scholar 

  8. Joosten LA, Netea MG, Fantuzzi G, Koenders MI, Helsen MM, Sparrer H, et al. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum. 2009;60(12):3651–62. doi:10.1002/art.25006.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Steele C, Rapaka RR, Metz A, Pop SM, Williams DL, Gordon S, et al. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog. 2005;1(4):e42.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Werner JL, Metz AE, Horn D, Schoeb TR, Hewitt MM, Schwiebert LM, et al. Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. J Immunol. 2009;182(8):4938–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Netea MG, Warris A, Van der Meer JW, Fenton MJ, Verver-Janssen TJ, Jacobs LE, et al. Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis. 2003;188(2):320–6.

    Article  CAS  PubMed  Google Scholar 

  12. Dinarello CA. Overview of the interleukin-1 family of ligands and receptors. Semin Immunol. 2013;25(6):389–93. doi:10.1016/j.smim.2013.10.001.

    Article  CAS  PubMed  Google Scholar 

  13. Edwards MR, Mukaida N, Johnson M, Johnston SL. IL-1beta induces IL-8 in bronchial cells via NF-kappaB and NF-IL6 transcription factors and can be suppressed by glucocorticoids. Pulm Pharmacol Ther. 2005;18(5):337–45. doi:10.1016/j.pupt.2004.12.015.

    Article  CAS  PubMed  Google Scholar 

  14. Schelenz S, Smith DA, Bancroft GJ. Cytokine and chemokine responses following pulmonary challenge with Aspergillus fumigatus: obligatory role of TNF-alpha and GM-CSF in neutrophil recruitment. Med Mycol. 1999;37(3):183–94.

    Article  CAS  PubMed  Google Scholar 

  15. Gresnigt MS, Becker KL, Smeekens SP, Jacobs CW, Joosten LA, van der Meer JW, et al. Aspergillus fumigatus-induced IL-22 is not restricted to a specific Th cell subset and is dependent on complement receptor 3. J Immunol. 2013;190(11):5629–39. doi:10.4049/jimmunol.1202601.

    Article  CAS  PubMed  Google Scholar 

  16. Gresnigt MS, Bozza S, Becker KL, Joosten LA, Abdollahi-Roodsaz S, van der Berg WB, et al. A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of interleukin-1 receptor antagonist. PLoS Pathog. 2014;10(3):e1003936. doi:10.1371/journal.ppat.1003936.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Karthikeyan RS, Leal SM Jr, Prajna NV, Dharmalingam K, Geiser DM, Pearlman E, et al. Expression of innate and adaptive immune mediators in human corneal tissue infected with Aspergillus or fusarium. J Infect Dis. 2011;204(6):942–50. doi:10.1093/infdis/jir426.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Romani L. Immunity to fungal infections. Nat Rev Immunol. 2011;11(4):275–88. doi:10.1038/nri2939.

    Article  CAS  PubMed  Google Scholar 

  19. Warris A, Netea MG, Verweij PE, Gaustad P, Kullberg BJ, Weemaes CM, et al. Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi. Med Mycol. 2005;43(7):613–21.

    Article  CAS  PubMed  Google Scholar 

  20. Becker KL, Gresnigt MS, Smeekens SP, Jacobs CW, Magis-Escurra C, Jaeger M et al. Pattern recognition pathways leading to a Th2 cytokine bias in ABPA patients. Clin Exp Allergy. doi:10.1111/cea.12354.

  21. Smith NL, Hankinson J, Simpson A, Bowyer P, Denning DW. A prominent role for the IL1 pathway and IL15 in susceptibility to chronic cavitary pulmonary aspergillosis. Clin Microbiol Infect. 2013;. doi:10.1111/1469-0691.12473.

    PubMed  Google Scholar 

  22. van de Veerdonk FL, Netea MG, Dinarello CA, Joosten LA. Inflammasome activation and IL-1beta and IL-18 processing during infection. Trends Immunol. 2011;32(3):110–6. doi:10.1016/j.it.2011.01.003.

    Article  PubMed  Google Scholar 

  23. Bellocchio S, Montagnoli C, Bozza S, Gaziano R, Rossi G, Mambula SS, et al. The contribution of the toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol. 2004;172(5):3059–69.

    Article  CAS  PubMed  Google Scholar 

  24. Obar J, Lehmann M, Caffrey A, Watschke C, Shepardson K, Barker B et al. IL-1α and IL-1β play non-redundant roles in limiting in vivo Aspergillus fumigatus pulmonary growth. J Immunol. 2013; 190(125.20).

  25. Lilly LM, Gessner MA, Dunaway CW, Metz AE, Schwiebert L, Weaver CT, et al. The beta-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. J Immunol. 2012;. doi:10.4049/jimmunol.1201797.

    PubMed Central  PubMed  Google Scholar 

  26. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 2011;117(14):3720–32. doi:10.1182/blood-2010-07-273417.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Fontaine T, Delangle A, Simenel C, Coddeville B, van Vliet SJ, van Kooyk Y, et al. Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus. PLoS Pathog. 2011;7(11):e1002372. doi:10.1371/journal.ppat.1002372.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Gravelat FN, Beauvais A, Liu H, Lee MJ, Snarr BD, Chen D, et al. Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal beta-glucan from the immune system. PLoS Pathog. 2013;9(8):e1003575. doi:10.1371/journal.ppat.1003575.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Rosen-Wolff A, Soldan W, Heyne K, Bickhardt J, Gahr M, Roesler J. Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization. Ann Hematol. 2001;80(2):113–5.

    Article  CAS  PubMed  Google Scholar 

  30. Morgenstern DE, Gifford MA, Li LL, Doerschuk CM, Dinauer MC. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J Exp Med. 1997;185(2):207–18.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Kyrmizi I, Gresnigt MS, Akoumianaki T, Samonis G, Sidiropoulos P, Boumpas D, et al. Corticosteroids block autophagy protein recruitment in Aspergillus fumigatus phagosomes via targeting dectin-1/Syk kinase signalling. J Immunol. 2013;191(3):1287–99. doi:10.4049/jimmunol.1300132.

    Article  CAS  PubMed  Google Scholar 

  32. de Luca A, Smeekens SP, Casagrande A, Iannitti R, Conway KL, Gresnigt MS, et al. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci U S A. 2014;111(9):3526–31. doi:10.1073/pnas.1322831111.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Ma J, Becker C, Lowell CA, Underhill DM. Dectin-1-triggered recruitment of light chain 3 protein to phagosomes facilitates major histocompatibility complex class II presentation of fungal-derived antigens. J Biol Chem. 2012;287(41):34149–56. doi:10.1074/jbc.M112.382812.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Sanjuan MA, Dillon CP, Tait SW, Moshiach S, Dorsey F, Connell S, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007;450(7173):1253–7. doi:10.1038/nature06421.

    Article  CAS  PubMed  Google Scholar 

  35. van de Veerdonk FL, Smeekens SP, Joosten LA, Kullberg BJ, Dinarello CA, van der Meer JW et al. Reactive oxygen species-independent activation of the IL-1beta inflammasome in cells from patients with chronic granulomatous disease. Proc Natl Acad Sci U S A. 107(7):3030–3.

  36. Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood. 2010;116(9):1570–3. doi:10.1182/blood-2010-01-264218.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Sainz J, Perez E, Gomez-Lopera S, Jurado M. IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level. J Clin Immunol. 2008;28(5):473–85. doi:10.1007/s10875-008-9197-0.

    Article  CAS  PubMed  Google Scholar 

  38. Dinarello C, Arend W, Sims J, Smith D, Blumberg H, O’Neill L, et al. IL-1 family nomenclature. Nat Immunol. 2010;11(11):973. doi:10.1038/ni1110-973.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Towne JE, Garka KE, Renshaw BR, Virca GD, Sims JE. Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem. 2004;279(14):13677–88. doi:10.1074/jbc.M400117200M400117200.

    Article  CAS  PubMed  Google Scholar 

  40. Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M, Gabel CA, et al. Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity. J Biol Chem. 2011;286(49):42594–602. doi:10.1074/jbc.M111.267922.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Gresnigt MS, Rosler B, Jacobs CW, Becker KL, Joosten LA, van der Meer JW, et al. The IL-36 receptor pathway regulates Aspergillus fumigatus-induced Th1 and Th17 responses. Eur J Immunol. 2013;43(2):416–26. doi:10.1002/eji.201242711.

    Article  CAS  PubMed  Google Scholar 

  42. van de Veerdonk FL, Stoeckman AK, Wu G, Boeckermann AN, Azam T, Netea MG, et al. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. Proc Natl Acad Sci U S A. 2012;109(8):3001–5. doi:10.1073/pnas.1121534109.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Kumar S, Hanning CR, Brigham-Burke MR, Rieman DJ, Lehr R, Khandekar S, et al. Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-gamma production. Cytokine. 2002;18(2):61–71.

    Article  CAS  PubMed  Google Scholar 

  44. Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010;11(11):1014–22. doi:10.1038/ni.1944.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, et al. IL1HY1: a novel interleukin-1 receptor antagonist gene. Biochem Biophys Res Commun. 1999;263(3):702–6. doi:10.1006/bbrc.1999.1440.

    Article  CAS  PubMed  Google Scholar 

  46. Ramadas RA, Ewart SL, Medoff BD, LeVine AM. Interleukin-1 family member 9 stimulates chemokine production and neutrophil influx in mouse lungs. Am J Respir Cell Mol Biol. 2011;44(2):134–45. doi:10.1165/rcmb.2009-0315OC.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Chustz RT, Nagarkar DR, Poposki JA, Favoreto S Jr, Avila PC, Schleimer RP, et al. Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2011;45(1):145–53. doi:10.1165/rcmb.2010-0075OC.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Ramadas RA, Li X, Shubitowski DM, Samineni S, Wills-Karp M, Ewart SL. IL-1 receptor antagonist as a positional candidate gene in a murine model of allergic asthma. Immunogenetics. 2006;58:851–5. doi:10.1007/s00251-006-0146-x.

    Article  CAS  PubMed  Google Scholar 

  49. Chen H, Wang Y, Bai C, Wang X. Alterations of plasma inflammatory biomarkers in the healthy and chronic obstructive pulmonary disease patients with or without acute exacerbation. J Proteomics. 2012;75:2835–43. doi:10.1016/j.jprot.2012.01.027.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

F. L. van de Veerdonk was supported by a Veni Grant of the Netherlands Organization for Scientific Research, and a NCMLS Grant from RUNMC.

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  1. Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands

    Mark S. Gresnigt & Frank L. van de Veerdonk

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Correspondence to Frank L. van de Veerdonk.

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Gresnigt, M.S., van de Veerdonk, F.L. The Role of Interleukin-1 Family Members in the Host Defence Against Aspergillus fumigatus . Mycopathologia 178, 395–401 (2014). https://doi.org/10.1007/s11046-014-9776-y

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