Immune evasion by acquisition of complement inhibitors: The mould Aspergillus binds both factor H and C4b binding protein

Vogl, G.; Lesiak, Iwona; Jensen, Dorthe Bødker; Perkhofer, Susanne; Eck, Raimund; Speth, Cornelia; Lass‐Flörl, Cornelia; Zipfel, Peter F.; Blom, Anna M.; Dierich, Manfred P.; Würzner, Reinhard

doi:10.1016/j.molimm.2007.08.011

Cited by 61 publications

(51 citation statements)

References 36 publications

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“…Protection from the alternative and the classical pathways by binding those complement inhibitors has been demonstrated for Neisseria gonorrhoeae (29,30), Streptococcus pyogenes (11,26), Candida albicans (23,24), Aspergillus fumigatus and Aspergillus terreus (36), and the relapsing fever spirochetes Borrelia recurrentis and Borrelia duttonii (21). As already mentioned, Meri et al demonstrated acquisition of factor H and FHR-1 by pathogenic leptospires (22).…”

Section: Fig 4 Deposition Of Complement Proteins On L Interrogansmentioning

confidence: 86%

Immune Evasion ofLeptospiraSpecies by Acquisition of Human Complement Regulator C4BP

et al. 2009

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Leptospirosis is a spirochetal zoonotic disease of global distribution with a high incidence in tropical regions. In the last 15 years it has been recognized as an important emerging infectious disease due to the occurrence of large outbreaks in warm-climate countries and, occasionally, in temperate regions. Pathogenic leptospires efficiently colonize target organs after penetrating the host. Their invasiveness is attributed to the ability to multiply in blood, adhere to host cells, and penetrate into tissues. Therefore, they must be able to evade the innate host defense. The main purpose of the present study was to evaluate how several Leptospira strains evade the protective function of the complement system. The serum resistance of six Leptospira strains was analyzed. We demonstrate that the pathogenic strain isolated from infected hamsters avoids serum bactericidal activity more efficiently than the culture-attenuated or the nonpathogenic Leptospira strains. Moreover, both the alternative and the classical pathways of complement seem to be responsible for the killing of leptospires. Serum-resistant and serum-intermediate strains are able to bind C4BP, whereas the serumsensitive strain Patoc I is not. Surface-bound C4BP promotes factor I-mediated cleavage of C4b. Accordingly, we found that pathogenic strains displayed reduced deposition of the late complement components C5 to C9 upon exposure to serum. We conclude that binding of C4BP contributes to leptospiral serum resistance against host complement.

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Section: Fig 4 Deposition Of Complement Proteins On L Interrogansmentioning

confidence: 86%

Immune Evasion ofLeptospiraSpecies by Acquisition of Human Complement Regulator C4BP

et al. 2009

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“…Sequestration of host C4BP as a strategy for complement evasion has been described for a number of pathogens, including (3,4,8,12,23,25,32,38,40,41,42,43,53), fungi (Candida albicans [30], Aspergillus fumigatus, and Aspergillus terreus [57]), and even the nematode Loa loa (20). To date, a few bacterial receptors have been shown to interact with C4BP.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of LcpA, a Surface-Exposed Protein ofLeptospiraspp. That Binds the Human Complement Regulator C4BP

et al. 2010

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We have previously shown that pathogenic leptospiral strains are able to bind C4b binding protein (C4BP). Surface-bound C4BP retains its cofactor activity, indicating that acquisition of this complement regulator may contribute to leptospiral serum resistance. In the present study, the abilities of seven recombinant putative leptospiral outer membrane proteins to interact with C4BP were evaluated. The protein encoded by LIC11947 interacted with this human complement regulator in a dose-dependent manner. The cofactor activity of C4BP bound to immobilized recombinant LIC11947 (rLIC11947) was confirmed by detecting factor I-mediated cleavage of C4b. rLIC11947 was therefore named LcpA (for leptospiral complement regulator-acquiring protein A). LcpA was shown to be an outer membrane protein by using immunoelectron microscopy, cell surface proteolysis, and Triton X-114 fractionation. The gene coding for LcpA is conserved among pathogenic leptospiral strains. This is the first characterization of a Leptospira surface protein that binds to the human complement regulator C4BP in a manner that allows this important regulator to control complement system activation mediated either by the classical pathway or by the lectin pathway. This newly identified protein may play a role in immune evasion by Leptospira spp. and may therefore represent a target for the development of a human vaccine against leptospirosis.

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“…The opportunistic human pathogenic fungi Candida albicans and Aspergillus fumigatus interact with the host complement system and bind the regulators CFH, CFHL1, and C4b-binding protein (6,14,(17)(18)(19). These regulators may limit complement activation on the fungal surface and reduce the amount of pathogenbound opsonins, thus influencing opsonophagocytosis.…”

mentioning

confidence: 99%

Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity

Losse¹,

Zipfel

Józsi³

2009

The Journal of Immunology

100

124

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The host complement system plays an important role in protection against infections. Several human-pathogenic microbes were shown to acquire host complement regulators, such as factor H (CFH), that downregulate complement activation at the microbial surface and protect the pathogens from the opsonic and lytic effects of complement. Because CFH can also bind to host cells, we addressed the role of CFH and CFH-related proteins as adhesion ligands in host-pathogen interactions. We show that the CFH family proteins CFH, CFH-like protein 1 (CFHL1), CFH-related protein (CFHR) 1, and CFHR4 long isoform bind to human neutrophil granulocytes and to the opportunistic human-pathogenic yeast Candida albicans. Two major binding sites, one within the N-terminus and one in the C-terminus of CFH, were found to mediate binding to neutrophils. Complement receptor 3 (CD11b/CD18; αMβ2 integrin) was identified as the major cellular receptor on neutrophils for CFH, CFHL1, and CFHR1, but not for CFHR4 long isoform. CFH and CFHR1 supported cell migration. Furthermore, CFH, CFHL1, and CFHR1 increased attachment of neutrophils to C. albicans. Adhesion of neutrophils to plasma-opsonized yeasts was reduced when CFH binding was inhibited by specific Abs or when using CFH-depleted plasma. Yeast-bound CFH and CFHR1 enhanced the generation of reactive oxygen species and the release of the antimicrobial protein lactoferrin by human neutrophils, and resulted in a more efficient killing of the pathogen. Thus, CFH and CFHR1, when bound on the surface of C. albicans, enhance antimicrobial activity of human neutrophils.

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Immune evasion by acquisition of complement inhibitors: The mould Aspergillus binds both factor H and C4b binding protein

Cited by 61 publications

References 36 publications

Immune Evasion ofLeptospiraSpecies by Acquisition of Human Complement Regulator C4BP

Immune Evasion ofLeptospiraSpecies by Acquisition of Human Complement Regulator C4BP

Functional Characterization of LcpA, a Surface-Exposed Protein ofLeptospiraspp. That Binds the Human Complement Regulator C4BP

Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity

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