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Semin Respir Crit Care Med 2004; 25(1): 63-71
DOI: 10.1055/s-2004-822306
DOI: 10.1055/s-2004-822306
Pulmonary Defenses Against Fungi
Further Information
Publication History
Publication Date:
12 March 2004 (online)
Pulmonary immunity to fungal pathogens requires both innate and adaptive immune responses. Alveolar macrophages, dendritic cells, and neutrophils are the phagocytic cells of the lung innate system. These cells produce early inflammatory mediators (i.e., reactive oxygen species, cytokines, and chemokines) in response to fungal infection. The production of early cytokines by innate cells, namely tumor necrosis factor alpha (TNF-α) and interleukin (IL)-12, plays a central role in the development of protective cell-mediated immunity against fungi. T helper 1 (Th1) cell-mediated immunity is essential for limiting a pulmonary fungal infection. Virulence factors produced by the fungi can also modulate the host immune response. Fungal virulence factors include the production of prostaglandins and a polysaccharide capsule.
The type of adaptive immune response (T1 vs T2) generated determines whether the fungi are cleared from the lungs or a chronic fungal infection prevails.
KEYWORDS
Fungi - pulmonary immunity - T1/T2 regulation
REFERENCES
- 1 Harrison T S. Cryptococcus neoformans and cryptococcosis. J Infect. 2000; 41 12-17
- 2 Newman S L. Cell-mediated immunity to Histoplasma capsulatum . Semin Respir Infect. 2001; 16 102-108
- 3 Latge J P. The pathobiology of Aspergillus fumigatus . Trends Microbiol. 2001; 9 382-389
- 4 Mansour M K, Levitz S M. Interactions of fungi with phagocytes. Curr Opin Microbiol. 2002; 5 359-365
- 5 Kawakami K, Tohyama M, Qifeng X, Saito A. Expression of cytokines and inducible nitric oxide synthase mRNA in the lungs of mice infected with Cryptococcus neoformans: effects of interleukin-12. Infect Immun. 1997; 65 1307-1312
- 6 Kawakami K, Qureshi M H, Koguchi Y et al.. Role of TNF-alpha in the induction of fungicidal activity of mouse peritoneal exudate cells against Cryptococcus neoformans by IL-12 and IL-18. Cell Immunol. 1999; 193 9-16
- 7 Qureshi M H, Zhang T, Koguchi Y et al.. Combined effects of IL-12 and IL-18 on the clinical course and local cytokine production in murine pulmonary infection with Cryptococcus neoformans . Eur J Immunol. 1999; 29 643-649
- 8 Deepe Jr G S. Immune response to early and late Histoplasma capsulatum infections. Curr Opin Microbiol. 2000; 3 359-362
- 9 Lipovsky M M, Gekker G, Hu S, Ehrlich L C, Hoepelman A I, Peterson P K. Cryptococcal glucuronoxylomannan induces interleukin (IL)-8 production by human microglia but inhibits neutrophil migration toward IL-8. J Infect Dis. 1998; 177 260-263
- 10 Lipovsky M M, Tsenova L, Coenjaerts F E, Kaplan G, Cherniak R, Hoepelman A I. Cryptococcal glucuronoxylomannan delays translocation of leukocytes across the blood-brain barrier in an animal model of acute bacterial meningitis. J Neuroimmunol. 2000; 111 10-14
- 11 Mambula S S, Simons E R, Hastey R, Selsted M E, Levits S M. Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans . Infect Immun. 2000; 68 6257-6264
- 12 Levitz S M, Farrell T P. Human neutrophil degranulation stimulated by Aspergillus fumigatus . J Leukoc Biol. 1990; 47 170-175
- 13 Cox R A, Magee D M. Protective immunity in coccidioidomycosis. Res Immunol. 1998; 149 417-428 , discussion 506-507
- 14 Meloni-Bruneri L H, Campa A, Abdalla D S, Calich V L, Lenzi H L, Burger E. Neutrophil oxidative metabolism and killing of Paracoccidioides brasiliensis after air pouch infection of susceptible and resistant mice. J Leukoc Biol. 1996; 59 526-533
- 15 Xidieh C F, Lenzi H L, Calich V L, Burger E. Influence of the genetic background on the pattern of lesions developed by resistant and susceptible mice infected with Paracoccidioides brasiliensis . Med Microbiol Immunol (Berl). 1999; 188 41-49
- 16 Zhou P, Miller G, Seder R A. Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-alpha plays a critical role in maintaining secondary immunity in the absence of IFN-gamma. J Immunol. 1998; 160 1359-1368
- 17 Clemons K V, Calich V L, Burger E et al.. Pathogenesis I: interactions of host cells and fungi. Med Mycol. 2000; 38(suppl 1) 99-111
- 18 Montagnoli C, Bacci A, Bozza S et al.. The plasticity of dendritic cells at the host/fungal interface. Immunobiology. 2001; 204 582-589
- 19 Gildea L A, Morris R E, Newman S L. Histoplasma capsulatum yeasts are phagocytosed via very late antigen-5, killed, and processed for antigen presentation by human dendritic cells. J Immunol. 2001; 166 1049-1056
- 20 Bozza S, Gaziano R, Spreca A et al.. Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus. J Immunol. 2002; 168 1362-1371
- 21 Syme R M, Spurrell J C, Amankwah E K, Green F H, Mody C H. Primary dendritic cells phagocytose Cryptococcus neoformans via mannose receptors and Fc gamma receptor II for presentation to T lymphocytes. Infect Immun. 2002; 70 5972-5981
- 22 d'Ostiani C F, DelSero 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. 2000; 191 1661-1674
- 23 Roilides E, Tsaparidou S, Kadiltsoglou I, Sein T, Walsh T J. Interleukin-12 enhances antifungal activity of human mononuclear phagocytes against Aspergillus fumigatus: implications for a gamma interferon-independent pathway. Infect Immun. 1999; 67 3047-3050
- 24 Grazziutti M, Przepiorko D, Rex J H, Braunschweig I, Vadham-Raj S, Savary C A. Dendritic cell-mediated stimulation of the in vitro lymphocyte response to Aspergillus. Bone Marrow Transplant. 2001; 27 647-652
- 25 Richards J O, Ampel N M, Galgiani J N, Lake D F. Dendritic cells pulsed with Coccidioides immitis lysate induce antigen-specific naive T cell activation. J Infect Dis. 2001; 184 1220-1224
- 26 Arsura E L, Bellinghausen P L, Kilgore W B, Abraham J J, Johnson R H. Septic shock in coccidioidomycosis. Crit Care Med. 1998; 26 62-65
- 27 Dooley D P, Cox R A, Hestilow K L, Dolan M J, Magee D M. Cytokine induction in human coccidioidomycosis. Infect Immun. 1994; 62 3980-3983
- 28 Finkel-Jimenez B, Wuthrich M, Brandhorst T, Klein B S. The WI-1 adhesin blocks phagocyte TNF-alpha production, imparting pathogenicity on Blastomyces dermatitidis . J Immunol. 2001; 166 2665-2673
- 29 Allendoerfer R, Deepe Jr G S. Regulation of infection with Histoplasma capsulatum by TNFR1 and -2. J Immunol. 2000; 165 2657-2664
- 30 Brieland J K, Jackson C, Menzel F et al.. Cytokine networking in lungs of immunocompetent mice in response to inhaled Aspergillus fumigatus . Infect Immun. 2001; 69 1554-1560
- 31 Huffnagle G B, Toews G B, Burdick M D, Boyd M B, McAllister K S, McDonald R A. Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans . J Immunol. 1996; 157 4529-4536
- 32 Hoffman O A, Standing J E, Limper A H. Pneumocystis carinii stimulates tumor necrosis factor-alpha release from alveolar macrophages through a beta-glucan-mediated mechanism. J Immunol. 1993; 150 3932-3940
- 33 Herring A C, Lee J, McDonald R A, Toews G B, Huffnagle G B. Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection. Infect Immun. 2002; 70 2959-2964
- 34 Chen W, Havell E A, Harmsen A G. Importance of endogenous tumor necrosis factor alpha and gamma interferon in host resistance against Pneumocystis carinii infection. Infect Immun. 1992; 60 1279-1284
- 35 Wood K L, Hage C A, Knox K S et al.. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003; 167 1279-1282
- 36 Warris A, Bjorneklett A, Gaustad P. Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med. 2001; 344 1099-1100
- 37 True D G, Penmetcha M, Peckham S J. Disseminated cryptococcal infection in rheumatoid arthritis treated with methotrexate and infliximab. J Rheumatol. 2002; 29 1561-1563
- 38 Tai T L, O'Rourke K P, McWeeney M, Burke C M, Sheehan K, Barry M. Pneumocystis carinii pneumonia following a second infusion of infliximab. Rheumatol. 2002; 41 951-952
- 39 Lee J H, Slifman N R, Gershon S K et al.. Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. Arthritis Rheum. 2002; 46 2565-2570
- 40 Zhou P, Seive M C, Bennett J, Kwon-Chung K J, Tewari R P, Gazzinelli R T. IL-12 prevents mortality in mice infected with Histoplasma capsulatum through induction of IFN-gamma. J Immunol. 1995; 155 785-795
- 41 Decken K, Kohler G, Palmer-Lehmann K et al.. Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans . Infect Immun. 1998; 66 4994-5000
- 42 Retini C, Kozel T R, Pietrella D, Monari C, Bistoni F, Vecchiarelli A. Interdependency of interleukin-10 and interleukin-12 in regulation of T-cell differentiation and effector function of monocytes in response to stimulation with Cryptococcus neoformans . Infect Immun. 2001; 69 6064-6073
- 43 Kawakami K, Hossain Qureshi M, Zhang T et al.. Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-gamma-inducing cytokines. Cell Immunol. 1999; 197 55-61
- 44 Allendoerfer R, Biovin G P, Deepe Jr G S. Modulation of immune responses in murine pulmonary histoplasmosis. J Infect Dis. 1997; 175 905-914
- 45 Deepe Jr G S, Gibbons R, Woodward E. Neutralization of endogenous granulocyte-macrophage colony-stimulating factor subverts the protective immune response to Histoplasma capsulatum . J Immunol. 1999; 163 4985-4993
- 46 Beenhouwer D O, Shapiro S, Feldmesser M, Casadevall A, Scharff M D. Both Th1 and Th2 cytokines affect the ability of monoclonal antibodies to protect mice against Cryptococcus neoformans . Infect Immun. 2001; 69 6445-6455
- 47 Traynor T R, Huffnagle G B. Role of chemokines in fungal infections. Med Mycol. 2001; 39 41-50
- 48 Mehrad B, Strieter R M, Moore T A, Tsai W C, Lira S A, Standiford T J. CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis. J Immunol. 1999; 163 6086-6094
- 49 Mehrad B, Moore T A, Standiford T J. Macrophage inflammatory protein-1 alpha is a critical mediator of host defense against invasive pulmonary aspergillosis in neutropenic hosts. J Immunol. 2000; 165 962-968
- 50 Huffnagle G B, Strieter R M, McNeil L K et al.. Macrophage inflammatory protein-1alpha (MIP-1alpha) is required for the efferent phase of pulmonary cell-mediated immunity to a Cryptococcus neoformans infection. J Immunol. 1997; 159 318-327
- 51 Traynor T R, Kuziel W A, Toews G B, Huffnagle G B. CCR2 expression determines T1 versus T2 polarization during pulmonary Cryptococcus neoformans infection. J Immunol. 2000; 164 2021-2027
- 52 Traynor T R, Herring A C, Dorf M E, Kuziel W A, Toews G B, Huffnagle G B. Differential roles of CC chemokine ligand 2/monocyte chemotactic protein-1 and CCR2 in the development of T1 immunity. J Immunol. 2002; 168 4659-4666
- 53 Vassallo R, Thomas Jr C F, Vuk-Pavlovic L, Limper A H. Mechanisms of defence in the lung: lessons from Pneumocystis carinii pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2000; 17 130-139
- 54 Harizi H, Gualde N. Dendritic cells produce eicosanoids, which modulate generation and functions of antigen-presenting cells. Prostaglandins Leukot Essent Fatty Acids. 2002; 66 459-466
- 55 Matsuoka T, Hirata M, Tanaka H et al.. Prostaglandin D2 as a mediator of allergic asthma. Science. 2000; 287 2013-2017
- 56 Demeure C E, Yang L P, Desjardins C, Raynauld P, Delespesse G. Prostaglandin E2 primes naive T cells for the production of anti-inflammatory cytokines. Eur J Immunol. 1997; 27 3526-3531
- 57 Noverr M C, Toews G B, Huffnagle G B. Production of prostaglandins and leukotrienes by pathogenic fungi. Infect Immun. 2002; 70 400-402
- 58 Noverr M C, Phare S M, Toews G B, Coffey M J, Huffnagle G B. Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect Immun. 2001; 69 2957-2963
- 59 Beck J M, Newbury R L, Palmer B E, Warnock M L, Byrd P K, Kaltreider H B. Role of CD8+ lymphocytes in host defense against Pneumocystis carinii in mice. J Lab Clin Med. 1996; 128 477-487
- 60 Harmsen A G, Stankiewicz M. Requirement for CD4+ cells in resistance to Pneumocystis carinii pneumonia in mice. J Exp Med. 1990; 172 937-945
- 61 Shellito J, Suzara V V, Blumenfeld W, Beck J M, Steger H J, Ermak T H. A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J Clin Invest. 1990; 85 1686-1693
- 62 Deepe Jr G S. Role of CD8+ T cells in host resistance to systemic infection with Histoplasma capsulatum in mice. J Immunol. 1994; 152 3491-3500
- 63 Cano L E, Singer-Vermes L M, Costa T A et al.. Depletion of CD8(+) T cells in vivo impairs host defense of mice resistant and susceptible to pulmonary paracoccidioidomycosis. Infect Immun. 2000; 68 352-359
- 64 Huffnagle G B, Yates J L, Lipscomb M F. Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells. J Exp Med. 1991; 173 793-800
- 65 Huffnagle G B, Lipscomb M F, Lovchik J A, Hoag K A, Street N E. The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection. J Leukoc Biol. 1994; 55 35-42
- 66 Mody C H, Lipscomb M F, Street N E, Toews G B. Depletion of CD4+ (L3T4+) lymphocytes in vivo impairs murine host defense to Cryptococcus neoformans . J Immunol. 1990; 144 1472-1477
- 67 Hill J O, Harmsen A G. Intrapulmonary growth and dissemination of an avirulent strain of Cryptococcus neoformans in mice depleted of CD4+ or CD8+ T cells. J Exp Med. 1991; 173 755-758
- 68 Mody C H, Chen G H, Jackson C, Curtis J L, Toews G B. Depletion of murine CD8+ T cells in vivo decreases pulmonary clearance of a moderately virulent strain of Cryptococcus neoformans . J Lab Clin Med. 1993; 121 765-773
- 69 Hoag K A, Street N E, Huffnagle G B, Lipscomb M F. Early cytokine production in pulmonary Cryptococcus neoformans infections distinguishes susceptible and resistant mice. Am J Respir Cell Mol Biol. 1995; 13 487-495
- 70 Brummer E, Hanson L H, Stevens D A. IL-4, IgE, and interferon-gamma production in pulmonary blastomycosis: comparison in mice untreated, immunized, or treated with an antifungal (SCH 39304). Cell Immunol. 1993; 149 258-267
- 71 Kashino S S, Fazioli R A, Cafalli-Favati C et al.. Resistance to Paracoccidioides brasiliensis infection is linked to a preferential Th1 immune response, whereas susceptibility is associated with absence of IFN-gamma production. J Interferon Cytokine Res. 2000; 20 89-97
- 72 Magee D M, Cox R A. Roles of gamma interferon and interleukin-4 in genetically determined resistance to Coccidioides immitis . Infect Immun. 1995; 63 3514-3519
- 73 Allendoerfer R, Deepe Jr G S. Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice. Infect Immun. 1997; 65 2564-2569
- 74 Cenci E, Mencacci A, DelSero G et al.. Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses. J Infect Dis. 1999; 180 1957-1968
- 75 Roilides E, Kadiltsoglou I, Dimitriadou A et al.. Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia. FEMS Immunol Med Microbiol. 1997; 19 169-180
- 76 Roilides E, Dimitriadou A, Kadiltsoglou I et al.. IL-10 exerts suppressive and enhancing effects on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus . J Immunol. 1997; 158 322-329
- 77 Huffnagle G B, Boyd M B, Street N E, Lipscomb M F. IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6). J Immunol. 1998; 160 2393-2400
- 78 McGuirk P, Mills K H. Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in immunity to infectious diseases. Trends Immunol. 2002; 23 450-455
- 79 McGuirk P, McCann C, Mills K H. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis . J Exp Med. 2002; 195 221-231
- 80 Hori S, Carvalho T L, Demengeot J. CD25+CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. Eur J Immunol. 2002; 32 1282-1291
- 81 Polonelli L, Casadevall A, Han Y et al.. The efficacy of acquired humoral and cellular immunity in the prevention and therapy of experimental fungal infections. Med Mycol. 2000; 38(suppl 1) 281-292
- 82 Casadevall A, Cassone A, Bistonei F et al.. Antibody and/or cell-mediated immunity, protective mechanisms in fungal disease: an ongoing dilemma or an unnecessary dispute?. Med Mycol. 1998; 36(suppl 1) 95-105
- 83 Casadevall A, Feldmesser M, Pirofski L A. Induced humoral immunity and vaccination against major human fungal pathogens. Curr Opin Microbiol. 2002; 5 386-391
- 84 Casadevall A. Passive antibody therapies: progress and continuing challenges. Clin Immunol. 1999; 93 5-15
- 85 Stevens D A, Kullberg B J, Brummer E, Casadevall A, Netea M G, Sugar A M. Combined treatment: antifungal drugs with antibodies, cytokines or drugs. Med Mycol. 2000; 38(suppl 1) 305-315
- 86 Langfelder K, Streibel M, Jahn B, Haase G, Brakhage A A. Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol. 2003; 38 143-158
- 87 Williamson P R. Laccase and melanin in the pathogenesis of Cryptococcus neoformans . Front Biosci. 1997; 2 e99-e107
- 88 Huffnagle G B, Chen G H, Curtis J L, McDonald R A, Streiter R M, Toews G B. Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation and immunity by a high melanin-producing strain of Cryptococcus neoformans . J Immunol. 1995; 155 3507-3516
- 89 Figueiredo F, Alves L M, Silva C L. Tumour necrosis factor production in vivo and in vitro in response to Paracoccidioides brasiliensis and the cell wall fractions thereof. Clin Exp Immunol. 1993; 93 189-194
- 90 Perfect J R, Wong B, Chang Y C, Kwon-Chung K J, Williamson P R. Cryptococcus neoformans: virulence and host defences. Med Mycol. 1998; 36(suppl 1) 79-86
- 91 Vecchiarelli A, Retini C, Pietrella D et al.. Downregulation by cryptococcal polysaccharide of tumor necrosis factor alpha and interleukin-1 beta secretion from human monocytes. Infect Immun. 1995; 63 2919-2923
- 92 Vecchiarelli A, Terini C, Monari C, Tascini C, Bistoni F, Kozel T R. Purified capsular polysaccharide of Cryptococcus neoformans induces interleukin-10 secretion by human monocytes. Infect Immun. 1996; 64 2846-2849
- 93 Monari C, Retini C, Palazzetti B, Bistoni F, Vecchiarelli A. Regulatory role of exogenous IL-10 in the development of immune response versus Cryptococcus neoformans . Clin Exp Immunol. 1997; 109 242-247
- 94 Collins H L, Bancroft G J. Encapsulation of Cryptococcus neoformans impairs antigen-specific T-cell responses. Infect Immun. 1991; 59(11) 3883-3888
Gary B HuffnaglePh.D.
Department of Internal Medicine-Pulmonary Division, 6301 MSRB III-box 0642, 1150 W.
Medical Center Dr., University of Michigan
Ann Arbor, MI 48109-0642
Email: ghuff@umich.edu