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Review

Cracking the Toll-like receptor code in fungal infections

, &
Pages 1121-1137 | Published online: 10 Jan 2014

References

  • Romani L. Overview of the fungal pathogens. In: Immunology of Infectious Diseases. Kaufman SHE, Sher A, Ahmed R (Eds). ASM Press, Washington DC, USA, 25–37 (2001).
  • Cooney NM, Klein BS. Fungal adaptation to the mammalian host: it is a new world, after all. Curr. Opin. Microbiol.11(6), 511–516 (2008).
  • Hube B. Fungal adaptation to the host environment. Curr. Opin. Microbiol.12(4), 347–349 (2009).
  • Antachopoulos C, Walsh TJ, Roilides E. Fungal infections in primary immunodeficiencies. Eur. J. Pediatr.166(11), 1099–1117 (2007).
  • Carneiro-Sampaio M, Coutinho A. Immunity to microbes: lessons from primary immunodeficiencies. Infect. Immun.75(4), 1545–1555 (2007).
  • Pappas PG, Alexander BD, Andes DR et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin. Infect. Dis.50(8), 1101–1111 (2010).
  • Kontoyiannis DP, Marr KA, Park BJ et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin. Infect. Dis.50(8), 1091–1100 (2010).
  • Singh N, Perfect JR. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect. Dis.7(6), 395–401 (2007).
  • Simon-Nobbe B, Denk U, Poll V, Rid R, Breitenbach M. The spectrum of fungal allergy. Int. Arch. Allergy Immunol.145(1), 58–86 (2008).
  • Denning DW, O’Driscoll BR, Hogaboam CM, Bowyer P, Niven RM. The link between fungi and severe asthma: a summary of the evidence. Eur. Respir. J.27(3), 615–626 (2006).
  • Romani L, Puccetti P. Immune regulation and tolerance to fungi in the lungs and skin. Chem. Immunol. Allergy94, 124–137 (2008).
  • Odds FC, Jacobsen MD. Multilocus sequence typing of pathogenic Candida species. Eukaryot. Cell7(7), 1075–1084 (2008).
  • Romani L. Immunity to fungal infections. Nat. Rev. Immunol.4(1), 1–23 (2004).
  • Shoham S, Levitz SM. The immune response to fungal infections. Br. J. Haematol.129(5), 569–582 (2005).
  • Romani L, Fallarino F, De Luca A et al. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature451(7175), 211–215 (2008).
  • Romani L, Puccetti P. Protective tolerance to fungi: the role of IL-10 and tryptophan catabolism. Trends Microbiol.14(4), 183–189 (2006).
  • Filipe-Santos O, Bustamante J, Chapgier A et al. Inborn errors of IL-12/23- and IFN-γ-mediated immunity: molecular, cellular, and clinical features. Semin. Immunol.18(6), 347–361 (2006).
  • Lilic D. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr. Opin. Infect. Dis.15(2), 143–147 (2002).
  • Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity30(5), 646–655 (2009).
  • Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu. Rev. Immunol.27, 485–517 (2009).
  • Dong C. Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat. Rev. Immunol.6(4), 329–333 (2006).
  • Romani L, Puccetti P. Controlling pathogenic inflammation to fungi. Expert Rev. Anti Infect. Ther.5(6), 1007–1017 (2007).
  • Carvalho A, Cunha C, Di Ianni M et al. Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation. Bone Marrow Transplant. DOI: 10.1038/bmt.2010.28 (2010) (Epub ahead of print).
  • Happel KI, Dubin PJ, Zheng M et al. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J. Exp. Med.202(6), 761–769 (2005).
  • Zelante T, De Luca A, Bonifazi P et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur. J. Immunol.37(10), 2695–2706 (2007).
  • De Luca A, Montagnoli C, Zelante T et al. Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J. Immunol.179(9), 5999–6008 (2007).
  • Heninger E, Hogan LH, Karman J et al. Characterization of the Histoplasma capsulatum-induced granuloma. J. Immunol.177(5), 3303–3313 (2006).
  • Leibundgut-Landmann S, Gross O, Robinson MJ et al. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol.8(6), 630–638 (2007).
  • van de Veerdonk FL, Marijnissen RJ, Kullberg BJ et al. The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe5(4), 329–340 (2009).
  • Kleinschek MA, Muller U, Brodie SJ et al. IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. J. Immunol.176(2), 1098–1106 (2006).
  • Rizzetto L, Kuka M, De Filippo C et al. Differential IL-17 production and mannan recognition contribute to fungal pathogenicity and commensalism. J. Immunol.184(8), 4258–4268 (2010).
  • Armstrong-James DP, Turnbull SA, Teo I et al. Impaired interferon-γ responses, increased interleukin-17 expression, and a tumor necrosis factor-α transcriptional program in invasive aspergillosis. J. Infect. Dis.200(8), 1341–1351 (2009).
  • Zhang Y, Wang F, Tompkins KC et al. Robust Th1 and Th17 immunity supports pulmonary clearance but cannot prevent systemic dissemination of highly virulent Cryptococcus neoformans H99. Am. J. Pathol.175(6), 2489–2500 (2009).
  • Fenoglio D, Poggi A, Catellani S et al. Vdelta1 T lymphocytes producing IFN-γ and IL-17 are expanded in HIV-1-infected patients and respond to Candida albicans. Blood113(26), 6611–6618 (2009).
  • Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat. Immunol.8(9), 942–949 (2007).
  • Bozza S, Clavaud C, Giovannini G et al. Immune sensing of Aspergillus fumigatus proteins, glycolipids, and polysaccharides and the impact on Th immunity and vaccination. J. Immunol.183, 2407–2414 (2009).
  • Chai LY, van de Veerdonk F, Marijnissen RJ et al. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity. Immunology130(1), 46–54 (2009).
  • Milner JD, Brenchley JM, Laurence A et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature452(7188), 773–776 (2008).
  • Ferwerda B, Ferwerda G, Plantinga TS et al. Human Dectin-1 deficiency and mucocutaneous fungal infections. N. Engl. J. Med.361(18), 1760–1767 (2009).
  • Conti HR, Shen F, Nayyar N et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med.206(2), 299–311 (2009).
  • Huang W, Na L, Fidel PL, Schwarzenberger P. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J. Infect. Dis.190(3), 624–631 (2004).
  • Zelante T, De Luca A, D’Angelo C, Moretti S, Romani L. IL-17/Th17 in anti-fungal immunity: what’s new? Eur. J. Immunol.39(3), 645–648 (2009).
  • De Luca A, Zelante T, D’Angelo C et al. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol.3(4), 361–373 (2010).
  • Romani L, Zelante T, De Luca A, Fallarino F, Puccetti P. IL-17 and therapeutic kynurenines in pathogenic inflammation to fungi. J. Immunol.180(8), 5157–5162 (2008).
  • Zenewicz LA, Flavell RA. IL-22 and inflammation: leukin’ through a glass onion. Eur. J. Immunol.38(12), 3265–3268 (2008).
  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell124(4), 783–801 (2006).
  • Gribar SC, Richardson WM, Sodhi CP, Hackam DJ. No longer an innocent bystander: epithelial Toll-like receptor signaling in the development of mucosal inflammation. Mol. Med.14(9–10), 645–659 (2008).
  • Weindl G, Naglik JR, Kaesler S et al. Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J. Clin. Invest.117(12), 3664–3672 (2007).
  • De Luca A, Bozza S, Zelante T et al. Nonhematopoietic cells contribute to protective tolerance to Aspergillus fumigatus via a TRIF pathway converging on IDO. Cell. Mol. Immunol. DOI:10.1038/cmi.2010.43 (2010) (Epub ahead of print).
  • Mayer AK, Bartz H, Fey F, Schmidt LM, Dalpke AH. Airway epithelial cells modify immune responses by inducing an anti-inflammatory microenvironment. Eur. J. Immunol.38(6), 1689–1699 (2008).
  • Balloy V, Sallenave JM, Wu Y et al.Aspergillus fumigatus-induced interleukin-8 synthesis by respiratory epithelial cells is controlled by the phosphatidylinositol 3-kinase, p38 MAPK, and ERK1/2 pathways and not by the Toll-like receptor-MyD88 pathway. J. Biol. Chem.283(45), 30513–30521 (2008).
  • Reaves TA, Chin AC, Parkos CA. Neutrophil transepithelial migration: role of Toll-like receptors in mucosal inflammation. Mem. Inst. Oswaldo Cruz100(Suppl. 1), 191–198 (2005).
  • Chignard M, Balloy V, Sallenave JM, Si-Tahar M. Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts. Clin. Immunol.124(3), 238–243 (2007).
  • Netea MG, Brown GD, Kullberg BJ, Gow NA. An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol.6(1), 67–78 (2008).
  • Romani L. Cell mediated immunity to fungi: a reassessment. Med. Mycol.46(6), 515–529 (2008).
  • Bellocchio S, Montagnoli C, Bozza S et al. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol.172(5), 3059–3069 (2004).
  • Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol.6(1), 33–43 (2006).
  • Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J.24(6), 1277–1286 (2005).
  • Saijo S, Fujikado N, Furuta T et al. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat. Immunol.8(1), 39–46 (2007).
  • Werner JL, Metz AE, Horn D et al. Requisite role for the Dectin-1 β-glucan receptor in pulmonary defense against Aspergillus fumigatus. J. Immunol.182(8), 4938–4946 (2009).
  • Gross O, Gewies A, Finger K et al. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature442(7103), 651–656 (2006).
  • Gringhuis SI, den Dunnen J, Litjens M et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk. Nat. Immunol.10(2), 203–213 (2009).
  • Heinsbroek SE, Brown GD, Gordon S. Dectin-1 escape by fungal dimorphism. Trends Immunol.26(7), 352–354 (2005).
  • Rappleye CA, Eissenberg LG, Goldman WE. Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor. Proc. Natl Acad. Sci. USA104(4), 1366–1370 (2007).
  • Plantinga TS, van der Velden WJ, Ferwerda B et al. Early stop polymorphism in human DECTIN-1 is associated with increased Candida colonization in hematopoietic stem cell transplant recipients. Clin. Infect. Dis.49(5), 724–732 (2009).
  • Lee HM, Yuk JM, Shin DM, Jo EK. Dectin-1 is inducible and plays an essential role for mycobacteria-induced innate immune responses in airway epithelial cells. J. Clin. Immunol.29(6), 795–805 (2009).
  • Bonifazi P, D’Angelo C, Zagarella S et al. Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis. Mucosal Immunol.3(2), 193–205 (2010).
  • Bonifazi P, Zelante T, D’Angelo C et al. Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal Immunol.2(4), 362–374 (2009).
  • Puccetti P, Grohmann U. IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-κB activation. Nat. Rev. Immunol.7(10), 817–823 (2007).
  • Bellocchio S, Moretti S, Perruccio K et al. TLRs govern neutrophil activity in aspergillosis. J. Immunol.173(12), 7406–7415 (2004).
  • van de Veerdonk FL, Kullberg BJ, van der Meer JW, Gow NA, Netea MG. Host–microbe interactions: innate pattern recognition of fungal pathogens. Curr. Opin. Microbiol.11(4), 305–312 (2008).
  • Behnsen J, Narang P, Hasenberg M et al. Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans. PLoS Pathog.3(2), e13 (2007).
  • 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 One5(4), e10008 (2010).
  • Kumar H, Kumagai Y, Tsuchida T et al. Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal β-glucan. J. Immunol.183(12), 8061–8067 (2009).
  • Gross O, Poeck H, Bscheider M et al. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature459(7245), 433–436 (2009).
  • Hise AG, Tomalka J, Ganesan S et al. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe5(5), 487–497 (2009).
  • Joly S, Ma N, Sadler JJ et al. Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J. Immunol.183(6), 3578–3581 (2009).
  • Lev-Sagie A, Prus D, Linhares IM et al. Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome. Am. J. Obstet. Gynecol.200(3), 303 e301–e306 (2009).
  • Bauernfeind FG, Horvath G, Stutz A et al. Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol.183(2), 787–791 (2009).
  • Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol.7(3), 179–190 (2007).
  • Chai LY, Kullberg BJ, Vonk AG et al. Modulation of Toll-like receptor 2 (TLR2) and TLR4 responses by Aspergillus fumigatus. Infect. Immun.77(5), 2184–2192 (2009).
  • 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. Cell86(6), 973–983 (1996).
  • Carvalho A, Cunha C, Pasqualotto AC et al. Genetic variability of innate immunity impacts human susceptibility to fungal diseases. Int. J. Infect. Dis.14(6), e460–e468 (2009).
  • Jouault T, Ibata-Ombetta S, Takeuchi O et al.Candida albicans phospholipomannan is sensed through Toll-like receptors. J. Infect. Dis.188(1), 165–172 (2003).
  • Netea MG, Van Der Graaf CA, Vonk AG et al. The role of to–ll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J. Infect. Dis.185(10), 1483–1489 (2002).
  • Villamon E, Gozalbo D, Roig P et al. Toll-like receptor-2 is essential in murine defenses against Candida albicans infections. Microbes Infect.6(1), 1–7 (2004).
  • Blasi E, Mucci A, Neglia R et al. Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans. FEMS Immunol. Med. Microbiol.44(1), 69–79 (2005).
  • Yanez A, Flores A, Murciano C et al. Signalling through TLR2/MyD88 induces differentiation of murine bone marrow stem and progenitor cells to functional phagocytes in response to Candida albicans. Cell. Microbiol.12(1), 114–128 (2010).
  • Netea MG, van de Veerdonk F, Verschueren I, van der Meer JW, Kullberg BJ. Role of TLR1 and TLR6 in the host defense against disseminated candidiasis. FEMS Immunol. Med. Microbiol.52(1), 118–123 (2008).
  • Wang JE, Warris A, Ellingsen EA et al. Involvement of CD14 and Toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae. Infect. Immun.69(4), 2402–2406 (2001).
  • Balloy V, Si-Tahar M, Takeuchi O et al. Involvement of Toll-like receptor 2 in experimental invasive pulmonary aspergillosis. Infect. Immun.73(9), 5420–5425 (2005).
  • Shoham S, Huang C, Chen JM, Golenbock DT, Levitz SM. Toll-like receptor 4 mediates intracellular signaling without TNF-α release in response to Cryptococcus neoformans polysaccharide capsule. J. Immunol.166(7), 4620–4626 (2001).
  • Biondo C, Midiri A, Messina L et al. MyD88 and TLR2, but not TLR4, are required for host defense against Cryptococcus neoformans. Eur. J. Immunol.35(3), 870–878 (2005).
  • Yauch LE, Mansour MK, Shoham S, Rottman JB, Levitz SM. Involvement of CD14, Toll-like receptors 2 and 4, and MyD88 in the host response to the fungal pathogen Cryptococcus neoformansin vivo. Infect. Immun.72(9), 5373–5382 (2004).
  • Loures FV, Pina A, Felonato M, Calich VL. TLR2 is a negative regulator of Th17 cells and tissue pathology in a pulmonary model of fungal infection. J. Immunol.183(2), 1279–1290 (2009).
  • Tada H, Nemoto E, Shimauchi H et al.Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor a by human monocytes in a CD14- and Toll-like receptor 4-dependent manner. Microbiol. Immunol.46(7), 503–512 (2002).
  • Netea MG, Gow NA, Munro CA et al. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J. Clin. Invest.116(6), 1642–1650 (2006).
  • Gasparoto TH, Tessarolli V, Garlet TP et al. Absence of functional TLR4 impairs response of macrophages after Candida albicans infection. Med. Mycol. DOI: 10.3109/13693786.2010.481292 (2010) (Epub ahead of print).
  • d’Ostiani CF, Del Sero G, Bacci A et al. Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans. Implications for initiation of T helper cell immunity in vitro and in vivo. J. Exp. Med.191(10), 1661–1674 (2000).
  • Villamon E, Gozalbo D, Roig P et al. Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida-induced production of cytokines. Eur. Cytokine Netw.15(3), 263–271 (2004).
  • Marr KA, Balajee SA, Hawn TR et al. Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens. Infect. Immun.71(9), 5280–5286 (2003).
  • Romani L, Bistoni F, Perruccio K et al. Thymosin α1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood108(7), 2265–2274 (2006).
  • Mambula SS, Sau K, Henneke P, Golenbock DT, Levitz SM. Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus. J. Biol. Chem.277(42), 39320–39326 (2002).
  • Bozza S, Zelante T, Moretti S et al. Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection. J. Immunol.180(6), 4022–4031 (2008).
  • Dubourdeau M, Athman R, Balloy V et al.Aspergillus fumigatus induces innate immune responses in alveolar macrophages through the MAPK pathway independently of TLR2 and TLR4. J. Immunol.177(6), 3994–4001 (2006).
  • Bretz C, Gersuk G, Knoblaugh S et al. MyD88 signaling contributes to early pulmonary responses to Aspergillus fumigatus. Infect. Immun.76(3), 952–958 (2008).
  • Rivera A, Ro G, Van Epps HL et al. Innate immune activation and CD4+ T cell priming during respiratory fungal infection. Immunity25(4), 665–675 (2006).
  • Ding K, Shibui A, Wang Y et al. Impaired recognition by Toll-like receptor 4 is responsible for exacerbated murine Pneumocystis pneumonia. Microbes Infect.7(2), 195–203 (2005).
  • Nakamura K, Miyagi K, Koguchi Y et al. Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans. FEMS Immunol. Med. Microbiol.47(1), 148–154 (2006).
  • Loures FV, Pina A, Felonato M et al. Toll-like receptor 4 signaling leads to severe fungal infection associated with enhanced proinflammatory immunity and impaired expansion of regulatory T cells. Infect. Immun.78(3), 1078–1088 (2010).
  • Miyazato A, Nakamura K, Yamamoto N et al. Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. Infect. Immun.77(7), 3056–3064 (2009).
  • Nakamura K, Miyazato A, Xiao G et al. Deoxynucleic acids from Cryptococcus neoformans activate myeloid dendritic cells via a TLR9-dependent pathway. J. Immunol.180(6), 4067–4074 (2008).
  • Ramirez-Ortiz ZG, Specht CA, Wang JP et al. Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA. Infect. Immun.76(5), 2123–2129 (2008).
  • Bozza S, Gaziano R, Lipford GB et al. Vaccination of mice against invasive aspergillosis with recombinant Aspergillus proteins and CpG oligodeoxynucleotides as adjuvants. Microbes Infect.4(13), 1281–1290 (2002).
  • Ramaprakash H, Ito T, Standiford TJ, Kunkel SL, Hogaboam CM. Toll-like receptor 9 modulates immune responses to Aspergillus fumigatus conidia in immunodeficient and allergic mice. Infect. Immun.77(1), 108–119 (2009).
  • Park SJ, Hughes MA, Burdick M, Strieter RM, Mehrad B. Early NK cell-derived IFN-γ is essential to host defense in neutropenic invasive aspergillosis. J. Immunol.182(7), 4306–4312 (2009).
  • Steele C, Rapaka RR, Metz A et al. The β-glucan receptor Dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog.1(4), e42 (2005).
  • Taylor PR, Tsoni SV, Willment JA et al. Dectin-1 is required for β-glucan recognition and control of fungal infection. Nat. Immunol.8(1), 31–38 (2007).
  • Nakamura K, Kinjo T, Saijo S et al. Dectin-1 is not required for the host defense to Cryptococcus neoformans. Microbiol. Immunol.51(11), 1115–1119 (2007).
  • Giles SS, Dagenais TR, Botts MR, Keller NP, Hull CM. Elucidating the pathogenesis of spores from the human fungal pathogen Cryptococcus neoformans. Infect. Immun.77(8), 3491–3500 (2009).
  • Bonfim CV, Mamoni RL, Blotta MH. TLR-2, TLR-4 and Dectin-1 expression in human monocytes and neutrophils stimulated by Paracoccidioides brasiliensis. Med. Mycol.47(7), 722–733 (2009).
  • Gow NA, Netea MG, Munro CA et al. Immune recognition of Candida albicans β-glucan by Dectin-1. J. Infect. Dis.196(10), 1565–1571 (2007).
  • Brown GD, Herre J, Williams DL et al. Dectin-1 mediates the biological effects of β-glucans. J. Exp. Med.197(9), 1119–1124 (2003).
  • Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by Dectin-1 and Toll-like receptor 2. J. Exp. Med.197(9), 1107–1117 (2003).
  • Dennehy KM, Ferwerda G, Faro-Trindade I et al. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur. J. Immunol.38(2), 500–506 (2008).
  • Dillon S, Agrawal S, Banerjee K et al. Yeast zymosan, a stimulus for TLR2 and Dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J. Clin. Invest.116(4), 916–928 (2006).
  • Luther K, Torosantucci A, Brakhage AA, Heesemann J, Ebel F. Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the Dectin-1 β-glucan receptor and Toll-like receptor 2. Cell Microbiol.9(2), 368–381 (2007).
  • Toyotome T, Adachi Y, Watanabe A et al. Activator protein 1 is triggered by Aspergillus fumigatus β-glucans surface-exposed during specific growth stages. Microb. Pathog.44(2), 141–150 (2008).
  • Jouault T, El Abed-El Behi M, Martinez-Esparza M et al. Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling. J. Immunol.177(7), 4679–4687 (2006).
  • Agrawal S, Agrawal A, Doughty B et al. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J. Immunol.171(10), 4984–4989 (2003).
  • Gringhuis SI, den Dunnen J, Litjens M et al. C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-κB. Immunity26(5), 605–616 (2007).
  • Garantziotis S, Hollingsworth JW, Zaas AK, Schwartz DA. The effect of Toll-like receptors and Toll-like receptor genetics in human disease. Annu. Rev. Med.59, 343–359 (2008).
  • Lasker MV, Nair SK. Intracellular TLR signaling: a structural perspective on human disease. J. Immunol.177(1), 11–16 (2006).
  • Rallabhandi P, Bell J, Boukhvalova MS et al. Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling. J. Immunol.177(1), 322–332 (2006).
  • Arbour NC, Lorenz E, Schutte BC et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet.25(2), 187–191 (2000).
  • Michel O, LeVan TD, Stern D et al. Systemic responsiveness to lipopolysaccharide and polymorphisms in the Toll-like receptor 4 gene in human beings. J. Allergy Clin. Immunol.112(5), 923–929 (2003).
  • Van der Graaf CA, Netea MG, Morre SA et al. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur. Cytokine Netw.17(1), 29–34 (2006).
  • van der Graaf CA, Netea MG, Drenth IP et al.Candida-specific interferon-γ deficiency and Toll-like receptor polymorphisms in patients with chronic mucocutaneous candidiasis. Neth. J. Med.61(11), 365–369 (2003).
  • Ryan KR, Hong M, Arkwright PD et al. Impaired dendritic cell maturation and cytokine production in patients with chronic mucocutanous candidiasis with or without APECED. Clin. Exp. Immunol.154(3), 406–414 (2008).
  • Roilides E, Anastasiou-Katsiardani A, Dimitriadou-Georgiadou A et al. Suppressive effects of interleukin-10 on human mononuclear phagocyte function against Candida albicans and Staphylococcus aureus. J. Infect. Dis.178(6), 1734–1742 (1998).
  • Del Sero G, Mencacci A, Cenci E et al. Antifungal type 1 responses are upregulated in IL-10-deficient mice. Microbes Infect.1(14), 1169–1180 (1999).
  • Morre SA, Murillo LS, Spaargaren J, Fennema HS, Pena AS. Role of the Toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection. J. Infect. Dis.186(9), 1377–1379; author reply 1379 (2002).
  • Netea MG, Sutmuller R, Hermann C et al. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J. Immunol.172(6), 3712–3718 (2004).
  • Woehrle T, Du W, Goetz A et al. Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans. Cytokine41(3), 322–329 (2008).
  • Carvalho A, Cunha C, Carotti A et al. Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation. Exp. Hematol.37(9), 1022–1029 (2009).
  • Carvalho A, Pasqualotto AC, Pitzurra L et al. Polymorphisms in Toll-like receptor genes and susceptibility to pulmonary aspergillosis. J. Infect. Dis.197(4), 618–621 (2008).
  • Kesh S, Mensah NY, Peterlongo P et al. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann. NY Acad. Sci.1062, 95–103 (2005).
  • Bochud PY, Chien JW, Marr KA et al. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N. Engl. J. Med.359(17), 1766–1777 (2008).
  • Kiechl S, Lorenz E, Reindl M et al. Toll-like receptor 4 polymorphisms and atherogenesis. N. Engl. J. Med.347(3), 185–192 (2002).
  • Ferwerda B, McCall MB, Alonso S et al. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc. Natl Acad. Sci. USA104(42), 16645–16650 (2007).
  • Glocker EO, Hennigs A, Nabavi M et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med.361(18), 1727–1735 (2009).
  • Cunha C, Di Ianni M, Bozza S 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 DOI 10.1182/blood-2010-04-279307 (2010) (Epub ahead of print).
  • de Vries HS, Plantinga TS, van Krieken JH et al. Genetic association analysis of the functional c.714T>G polymorphism and mucosal expression of Dectin-1 in inflammatory bowel disease. PLoS One4(11), e7818 (2009).
  • Romagne F. Current and future drugs targeting one class of innate immunity receptors: the Toll-like receptors. Drug Discov. Today12(1–2), 80–87 (2007).
  • McKinley L, Logar AJ, McAllister F et al. Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of pneumocystis pneumonia. J. Immunol.177(9), 6215–6226 (2006).
  • Montagnoli C, Bacci A, Bozza S et al. B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J. Immunol.169(11), 6298–6308 (2002).
  • Montagnoli C, Fallarino F, Gaziano R et al. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J. Immunol.176(3), 1712–1723 (2006).
  • Cavassani KA, Campanelli AP, Moreira AP et al. Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans. J. Immunol.177(9), 5811–5818 (2006).
  • Ezekowitz RA, Sastry K, Bailly P, Warner A. Molecular characterization of the human macrophage mannose receptor: demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells. J. Exp. Med.172(6), 1785–1794 (1990).
  • McGreal EP, Rosas M, Brown GD et al. The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose. Glycobiology16(5), 422–430 (2006).
  • Cambi A, Gijzen K, de Vries JM et al. The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells. Eur. J. Immunol.33(2), 532–538 (2003).
  • Edwards L, Williams AE, Krieg AM et al. Stimulation via Toll-like receptor 9 reduces Cryptococcus neoformans-induced pulmonary inflammation in an IL-12-dependent manner. Eur. J. Immunol.35(1), 273–281 (2005).
  • Netea MG, Van der Meer JW, Kullberg BJ. Toll-like receptors as an escape mechanism from the host defense. Trends Microbiol.12(11), 484–488 (2004).
  • Bellocchio S, Gaziano R, Bozza S et al. Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signalling from TLR-2 to TLR-4. J. Antimicrob. Chemother.55(2), 214–222 (2005).
  • Sau K, Mambula SS, Latz E et al. The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism. J. Biol. Chem.278(39), 37561–37568 (2003).

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