Home LiteratureArticle Details
PMID: 8665475 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Activation of the complement system by pathogenic fungi.

Clinical microbiology reviews ·Vol. 9 ·No. 1 ·1996-01-00 ·Pages 34-46

Kozel TR

Abstract

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

MeSH Terms
Aspergillosis/immunology Candidiasis/immunology Complement Activation Complement C3/chemistry Complement Pathway, Alternative Complement Pathway, Classical Cryptococcosis/immunology Fungi/immunology,pathogenicity Kinetics Mycoses/immunology
Chemicals
Complement C3
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kozel T R
Department of Microbiology and Cell and Molecular Biology Program, University of Nevada, Reno 89557, USA.
References (102)
102 references, click to expand
  1. Location of mannan and chitin on thin sections of budding yeasts with gold markers.
    Arch Microbiol. 1977 Oct 24;115(1):1-7 PMID: 337918
  2. Protective murine monoclonal antibodies to Cryptococcus neoformans.
    Infect Immun. 1992 Nov;60(11):4534-41 PMID: 1398966
  3. Role of complement in host defense against experimental disseminated candidiasis.
    J Infect Dis. 1978 Jul;138(1):9-16 PMID: 355578
  4. Chemotaxigenic activity of extracts from the mycelial and spherule phases of Coccidioides immitis for human polymorphonuclear leukocytes.
    Infect Immun. 1978 Sep;21(3):862-5 PMID: 711340
  5. Alternative pathway of complement activation by Candida albicans.
    Aust N Z J Med. 1978 Dec;8(6):620-2 PMID: 373736
  6. Evidence for an ester linkage between the labile binding site of C3b and receptive surfaces.
    J Immunol. 1979 Sep;123(3):1388-94 PMID: 38283
  7. Chemotaxigenesis and activation of the alternative complement pathway by encapsulated and non-encapsulated Cryptococcus neoformans.
    Infect Immun. 1979 Nov;26(2):435-40 PMID: 397927
  8. Comparison by ELISA of serum anti-Candida albicans mannan IgG levels of a normal population and in diseased patients.
    Mycopathologia. 1980 Mar 17;70(2):89-93 PMID: 6993953
  9. Complement activation by Coccidioides immitis: in vitro and clinical studies.
    Infect Immun. 1980 Jun;28(3):944-9 PMID: 6901703
  10. Activation of the alternative complement pathway by Histoplasma capsulatum.
    Infect Immun. 1980 Oct;30(1):147-9 PMID: 7439970
  11. Structure and antigenic activity of the capsular polysaccharide of Cryptococcus neoformans serotype A.
    Mol Immunol. 1980 Aug;17(8):1025-32 PMID: 6777664
  12. In vitro studies of the interaction of murine phagocytic cells with Candida albicans.
    J Reticuloendothel Soc. 1981 Jan;29(1):23-34 PMID: 7009855
  13. Genetic control of susceptibility to Cryptococcus neoformans in mice.
    Infect Immun. 1980 Aug;29(2):494-9 PMID: 7216421
  14. The immunofluorescence staining of fungi in chronic dermatophyte infections.
    Clin Exp Dermatol. 1981 Mar;6(2):155-8 PMID: 7021018
  15. Roles of macrophage Fc and C3b receptors in phagocytosis of immunologically coated Cryptococcus neoformans.
    Proc Natl Acad Sci U S A. 1981 Jun;78(6):3853-7 PMID: 7022456
  16. Immunization and complement interaction in host defense against murine Cryptococcosis.
    J Reticuloendothel Soc. 1981 Nov;30(5):347-57 PMID: 7320995
  17. Binding reaction between the third human complement protein and small molecules.
    Biochemistry. 1981 Dec 22;20(26):7457-63 PMID: 7326238
  18. Opsonic requirements for the uptake of Cryptococcus neoformans by human polymorphonuclear leukocytes and monocytes.
    J Infect Dis. 1982 Jun;145(6):870-4 PMID: 7045251
  19. Binding of C3b proceeds by a transesterification reaction at the thiolester site.
    Nature. 1982 Jul 1;298(5869):72-5 PMID: 6806664
  20. Requirement for an additional serum factor essential for the antibody-independent activation of the classical complement sequence by Gram-negative bacteria.
    Infect Immun. 1982 Sep;37(3):935-9 PMID: 6752030
  21. Chemotaxis of human neutrophils and monocytes induced by Cryptococcus neoformans.
    Infect Immun. 1982 Oct;38(1):380-2 PMID: 6754617
  22. Immune responses to Candida albicans in genetically distinct mice.
    Infect Immun. 1982 Dec;38(3):1020-8 PMID: 6759403
  23. Complement activation by trichophyton rubrum.
    J Invest Dermatol. 1983 Mar;80(3):156-8 PMID: 6827124
  24. Analysis of transepidermal leukocyte chemotaxis in experimental dermatophytosis in guinea pigs.
    Arch Dermatol Res. 1982;273(3-4):205-17 PMID: 7165350
  25. Kinetic and thermodynamic analysis of the control of C3b by the complement regulatory proteins factors H and I.
    Biochemistry. 1983 Jan 4;22(1):178-85 PMID: 6219696
  26. Localization on encapsulated Cryptococcus neoformans of serum components opsonic for phagocytosis by macrophages and neutrophils.
    Infect Immun. 1984 Feb;43(2):574-9 PMID: 6363293
  27. Cobra venom factor: structural homology with the third component of human complement.
    J Immunol. 1984 Dec;133(6):3235-41 PMID: 6491285
  28. The alternative pathway of complement.
    Springer Semin Immunopathol. 1984;7(2-3):163-92 PMID: 6238433
  29. Species specificity of recognition by the alternative pathway of complement.
    J Immunol. 1985 Feb;134(2):1101-4 PMID: 3155536
  30. PMN chemotactic factor produced by glass-adherent cells in the acute inflammation caused by Paracoccidioides brasiliensis.
    Br J Exp Pathol. 1985 Feb;66(1):57-65 PMID: 3882118
  31. The classical complement pathway: activation and regulation of the first complement component.
    Adv Immunol. 1985;37:151-216 PMID: 3890478
  32. Cutaneous cryptococcosis--a case with C3 deposition on capsules.
    J Dermatol. 1985 Feb;12(1):79-84 PMID: 3894461
  33. Activation of human complement system in paracoccidioidomycosis.
    J Med Vet Mycol. 1992;30(4):317-21 PMID: 1432491
  34. Activation of human complement system Paracoccidioides brasiliensis and its deposition on the yeast form cell surface.
    J Med Vet Mycol. 1992;30(6):481-4 PMID: 1287168
  35. Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans.
    Infect Immun. 1993 Jul;61(7):2966-72 PMID: 8514401
  36. Complement binding to Aspergillus conidia correlates with pathogenicity.
    J Lab Clin Med. 1993 Jul;122(1):27-35 PMID: 8320488
  37. Accelerated decay of C3b to iC3b when C3b is bound to the Cryptococcus neoformans capsule.
    Infect Immun. 1993 Oct;61(10):4360-6 PMID: 8406826
  38. Role for C5 and neutrophils in the pulmonary intravascular clearance of circulating Cryptococcus neoformans.
    Am J Respir Cell Mol Biol. 1993 Dec;9(6):617-27 PMID: 8257594
  39. Occurrences, specificities, and functions of ubiquitous antibodies in human serum that are reactive with the Cryptococcus neoformans cell wall.
    Infect Immun. 1994 Jan;62(1):215-20 PMID: 8262630
  40. Comparative pathogenesis of clinical and nonclinical isolates of Saccharomyces cerevisiae.
    J Infect Dis. 1994 Apr;169(4):859-67 PMID: 8133102
  41. Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan.
    Infect Immun. 1994 Jul;62(7):2857-64 PMID: 8005676
  42. Specificity of the thioester-containing reactive site of human C3 and its significance to complement activation.
    Biochem J. 1994 Sep 1;302 ( Pt 2):429-36 PMID: 8092994
  43. Classical and alternative complement pathway activation in paracoccidioidomycosis.
    J Investig Allergol Clin Immunol. 1994 Mar-Apr;4(2):91-5 PMID: 7921333
  44. Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell.
    J Exp Med. 1995 Jan 1;181(1):405-9 PMID: 7807020
  45. Pathogenicity of Saccharomyces cerevisiae in complement factor five-deficient mice.
    Infect Immun. 1995 Feb;63(2):478-85 PMID: 7822013
  46. The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena.
    Science. 1954 Aug 20;120(3112):279-85 PMID: 13186838
  47. On the composition of zymosan.
    Science. 1958 Apr 4;127(3301):756-7 PMID: 13543326
  48. Natural host resistance to infection with Cryptococcus neoformans. I. The effect of the properdin system on the experimental disease.
    J Infect Dis. 1961 Sep-Oct;109:147-53 PMID: 13896119
  49. Activity of mouse complement.
    J Immunol. 1962 Dec;89:861-7 PMID: 13974902
  50. DISTRIBUTION, INHERITANCE, AND PROPERTIES OF AN ANTIGEN, MUB1, AND ITS RELATION TO HEMOLYTIC COMPLEMENT.
    J Exp Med. 1964 Nov 1;120:897-924 PMID: 14247728
  51. Deficiency of the fifth component of complement in mice with an inherited complement defect.
    J Exp Med. 1967 Jan 1;125(1):1-16 PMID: 4959665
  52. Immunofluorescence studies of reactions at the Cryptococcal capsule.
    J Infect Dis. 1968 Apr;118(2):215-29 PMID: 4870973
  53. Surface characteristics of Aspergillus conidia.
    Mycologia. 1969 May-Jun;61(3):560-71 PMID: 5812249
  54. Genetically controlled total deficiency of the fourth component of complement in the guinea pig.
    Science. 1970 Oct 2;170(3953):74-5 PMID: 4989151
  55. Isolation of the anticomplementary protein from cobra venom and its mode of action on C3.
    J Immunol. 1971 Dec;107(6):1666-72 PMID: 5120401
  56. In vitro phagocytosis and intracellular fate of variously encapsulated strains of Cryptococcus neoformans.
    Infect Immun. 1972 Apr;5(4):491-8 PMID: 4564677
  57. Candida albicans and the chemotaxis of polymorphonuclear neutrophils.
    Sabouraudia. 1973 Nov;11(3):210-21 PMID: 4587891
  58. The role of late complement components and the alternate complement pathway in experimental cryptococcosis.
    Proc Soc Exp Biol Med. 1973 Oct 1;144(1):312-5 PMID: 4129497
  59. The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection.
    J Immunol. 1974 Jun;112(6):2260-70 PMID: 4596700
  60. Hemolytic, cytotoxic and complement inactivating properties of extracts of different species of Aspergillus.
    Mycopathologia. 1975 Dec 8;57(1):23-6 PMID: 813147
  61. Deposition of complement components in the cutaneous lesions of chronic mucocutaneous candidiasis.
    Clin Immunol Immunopathol. 1976 May;5(3):340-50 PMID: 776472
  62. Activation of the alternative (properdin) pathway of complement by Candida albicans and related species.
    J Invest Dermatol. 1976 Dec;67(6):700-3 PMID: 794419
  63. Deposition of complement in the lesions of experimental cutaneous candidiasis in guinea pigs.
    J Cutan Pathol. 1976;3(5):232-8 PMID: 1018063
  64. Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution.
    J Exp Med. 1977 Jul 1;146(1):257-70 PMID: 301546
  65. Interaction between the third complement protein and cell surface macromolecules.
    Proc Natl Acad Sci U S A. 1977 Jul;74(7):2701-5 PMID: 268620
  66. Experimental cutaneous candidiasis in rodents; II. Role of the stratum corneum barrier and serum complement as a mediator of a protective infalmmatory response.
    Arch Dermatol. 1978 Apr;114(4):539-43 PMID: 646364
  67. Complement depletion in cryptococcal sepsis.
    J Immunol. 1978 May;120(5):1686-90 PMID: 351055
  68. Isolation and characterization of a mannan-binding protein from rabbit liver.
    Biochem Biophys Res Commun. 1978 Apr 14;81(3):1018-24 PMID: 666781
  69. Ultrastructure of the cell wall of Candida albicans blastospores: study of its constitutive layers by the use of a cytochemical technique revealing polysaccharides.
    Ann Microbiol (Paris). 1978 Feb-Mar;129(2):141-53 PMID: 354457
  70. Contribution of complement component C5 to the pathogenesis of experimental murine cryptococcosis.
    Sabouraudia. 1985 Jun;23(3):225-34 PMID: 4023888
  71. The role of C5 in experimental murine paracoccidioidomycosis.
    J Infect Dis. 1985 Aug;152(2):425 PMID: 4031553
  72. Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b.
    Infect Immun. 1985 Nov;50(2):598-600 PMID: 2932390
  73. Activation of the complement system by Cryptococcus neoformans leads to binding of iC3b to the yeast.
    Infect Immun. 1986 Apr;52(1):1-5 PMID: 3514450
  74. Polymorphonuclear leukocytes, complement, and Trichophyton rubrum.
    J Invest Dermatol. 1986 Feb;86(2):138-41 PMID: 3745941
  75. Expression of specific binding sites on Candida with functional and antigenic characteristics of human complement receptors.
    J Immunol. 1986 Dec 1;137(11):3577-83 PMID: 2946764
  76. Inhibition of complement by culture supernatants of Aspergillus fumigatus.
    J Infect Dis. 1986 Dec;154(6):944-51 PMID: 3537152
  77. Activation and binding of C3 by Candida albicans.
    Infect Immun. 1987 Aug;55(8):1890-4 PMID: 3301679
  78. An iC3b receptor on Candida albicans: structure, function, and correlates for pathogenicity.
    J Infect Dis. 1988 Jan;157(1):38-46 PMID: 2961817
  79. Strain variation in phagocytosis of Cryptococcus neoformans: dissociation of susceptibility to phagocytosis from activation and binding of opsonic fragments of C3.
    Infect Immun. 1988 Nov;56(11):2794-800 PMID: 3049374
  80. C3bi-binding protein on Candida albicans: temperature-dependent expression and relationship to human complement receptor type 3.
    Infect Immun. 1989 Feb;57(2):616-22 PMID: 2521478
  81. Activation and binding of opsonic fragments of C3 on encapsulated Cryptococcus neoformans by using an alternative complement pathway reconstituted from six isolated proteins.
    Infect Immun. 1989 Jul;57(7):1922-7 PMID: 2525113
  82. Activation of C3 and binding to Aspergillus fumigatus conidia and hyphae.
    Infect Immun. 1989 Nov;57(11):3412-7 PMID: 2680973
  83. The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein.
    J Biol Chem. 1990 Feb 5;265(4):1980-4 PMID: 2298734
  84. Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q.
    J Immunol. 1990 Mar 15;144(6):2287-94 PMID: 2313094
  85. Reduced expression of the functionally active complement receptor for iC3b but not for C3d on an avirulent mutant of Candida albicans.
    Infect Immun. 1990 Apr;58(4):909-13 PMID: 2138588
  86. The iC3b receptor on Candida albicans: subcellular localization and modulation of receptor expression by glucose.
    J Infect Dis. 1990 Apr;161(4):761-8 PMID: 2138655
  87. Use of DBA/2N mice in models of systemic candidiasis and pulmonary and systemic aspergillosis.
    Infect Immun. 1990 May;58(5):1476-8 PMID: 2323826
  88. Cell-wall glucans of Cryptococcus neoformans Cap 67.
    Carbohydr Res. 1990 Apr 2;198(1):23-38 PMID: 2191777
  89. Fungal cell wall synthesis: the construction of a biological structure.
    Microbiol Sci. 1988 Dec;5(12):370-5 PMID: 3079180
  90. Aspergillus fumigatus complement inhibitor: production, characterization, and purification by hydrophobic interaction and thin-layer chromatography.
    Infect Immun. 1990 Nov;58(11):3508-15 PMID: 2228221
  91. Binding of Cryptococcus neoformans by human cultured macrophages. Requirements for multiple complement receptors and actin.
    J Clin Invest. 1991 Feb;87(2):528-35 PMID: 1991837
  92. In vivo anti-complementary activities of the cobra venom factors from Naja naja and Naja haje.
    J Immunol Methods. 1991 Feb 15;136(2):287-94 PMID: 1999656
  93. Molecular mimicry in Candida albicans. Role of an integrin analogue in adhesion of the yeast to human endothelium.
    J Clin Invest. 1991 Jun;87(6):1896-902 PMID: 2040685
  94. Differences in Cryptococcus neoformans capsular polysaccharide structure influence assembly of alternative complement pathway C3 convertase on fungal surfaces.
    Mol Immunol. 1991 Apr-May;28(4-5):465-70 PMID: 2062324
  95. Early events in initiation of alternative complement pathway activation by the capsule of Cryptococcus neoformans.
    Infect Immun. 1991 Sep;59(9):3101-10 PMID: 1831795
  96. Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity.
    Infect Immun. 1991 Oct;59(10):3700-7 PMID: 1716613
  97. Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans.
    Infect Immun. 1992 Mar;60(3):754-61 PMID: 1541548
  98. Interactions between conidia of Aspergillus fumigatus and human complement component C3.
    Infect Immun. 1992 May;60(5):1913-8 PMID: 1563783
  99. A role for complement receptor-like molecules in iron acquisition by Candida albicans.
    J Exp Med. 1992 Jun 1;175(6):1643-51 PMID: 1588285
  100. Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans.
    Eur J Immunol. 1992 Jun;22(6):1447-54 PMID: 1601035
  101. In vivo complement activation and binding of C3 to encapsulated Cryptococcus neoformans.
    Infect Immun. 1992 Sep;60(9):3937-9 PMID: 1500204
  102. Participation of complement in the phagocytosis of the conidia of Aspergillus fumigatus by human polymorphonuclear cells.
    J Infect Dis. 1992 Sep;166(3):580-6 PMID: 1500740
Article Info
Journal
Clinical microbiology reviews
Abbr.
Clin Microbiol Rev
ISSN
0893-8512
DOI
10.1128/CMR.9.1.34
Published
1996-01-00
Pages
34-46
Language
English
Region
United States
NLM ID
8807282
PMCID
PMC172880
Subset
IM
Grants
NIAID NIH HHS · AI 14209 · United States
NIAID NIH HHS · AI 31696 · United States
NIAID NIH HHS · AI 37194 · United States
External Links
PubMed source DOI: 10.1128/CMR.9.1.34 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2