Complement evasion of pathogens: Common strategies are shared by diverse organisms

Zipfel, Peter F.; Würzner, Reinhard; Skerka, Christine

doi:10.1016/j.molimm.2007.06.149

Cited by 154 publications

(129 citation statements)

References 49 publications

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“…1B; e.g. Oppermann et al , 2006; Józsi et al , 2007; Meri et al , 2013; reviewed in Zipfel et al , 2007, 2008, 2013; Józsi and Zipfel, 2008; Skerka and Zipfel, 2008; Ferreira et al , 2010). Interestingly, FH binding via CCP20 enhances C3b binding to FH and initiates the formation of a tripartite complex between FH, C3b and the microbial receptor, which then enhances the C3b‐inactiving activity of FH (Meri et al , 2013).…”

Section: Discussionmentioning

confidence: 99%

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ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

Rosa

Flammersfeld

Ngwa

et al. 2015

Cellular Microbiology

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SummaryThe acquisition of regulatory proteins is a means of blood‐borne pathogens to avoid destruction by the human complement. We recently showed that the gametes of the human malaria parasite Plasmodium falciparum bind factor H (FH) from the blood meal of the mosquito vector to assure successful sexual reproduction, which takes places in the mosquito midgut. While these findings provided a first glimpse of a complex mechanism used by Plasmodium to control the host immune attack, it is hitherto not known, how the pathogenic blood stages of the malaria parasite evade destruction by the human complement. We now show that the human complement system represents a severe threat for the replicating blood stages, particularly for the reinvading merozoites, with complement factor C3b accumulating on the surfaces of the intraerythrocytic schizonts as well as of free merozoites. C3b accumulation initiates terminal complement complex formation, in consequence resulting in blood stage lysis. To inactivate C3b, the parasites bind FH as well as related proteins FHL‐1 and CFHR‐1 to their surface, and FH binding is trypsin‐resistant. Schizonts acquire FH via two contact sites, which involve CCP modules 5 and 20. Blockage of FH‐mediated protection via anti‐FH antibodies results in significantly impaired blood stage replication, pointing to the plasmodial complement evasion machinery as a promising malaria vaccine target.

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Section: Discussionmentioning

confidence: 99%

“…meningitides for complement evasion (e.g. Poltermann et al , 2007; Malito et al , 2013; reviewed in Zipfel et al , 2007). …”

Section: Discussionmentioning

confidence: 99%

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

Rosa

Flammersfeld

Ngwa

et al. 2015

Cellular Microbiology

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“…Some bacterial pathogens evade complement-mediated destruction by binding FH, a negative regulator of the complement cascade (47). Although several bacterial binding proteins have been identified (17), the molecular basis of their interaction with FH is poorly defined.…”

Section: Discussionmentioning

confidence: 99%

Structure of Factor H-binding Protein B (FhbB) of the Periopathogen, Treponema denticola

Miller

Bell

McDowell

et al. 2012

Journal of Biological Chemistry

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Background:The Treponema denticola FhbB protein binds FH, a complement regulator. Results: The structure of FhbB was solved, and its interaction with FH was further defined. Conclusion: The structurally unique FhbB protein interacts with CCP7 of FH through electrostatic interactions. Significance: The T. denticola/FH interaction may perturb complement regulation resulting in conditions that favor the development of periodontal disease.

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“…Likely all successful infectious microbes have developed mechanisms to subvert or evade host complement attack by binding or mimicking complement proteins. 11 For example, Neisseria meningitidis specifically survive in human hosts and express proteins that bind to human negative regulators of the complement system such as complement factor H (CFH) in order to protect themselves from complement attack. 12 A selection pressure is therefore exerted on the microbe, which evolves quickly due to its short generation time, to successfully deceive the host immune system.…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Complement in age-related macular degeneration: a focus on function

Bradley

Zipfel

Hughes

2011

Eye

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Age-related macular degeneration (AMD) is an inflammatory disease, which causes visual impairment and blindness in older people. The proteins of the complement system are central to the development of this disease. Local and systemic inflammation in AMD are mediated by the deregulated action of the alternative pathway of the complement system. Variants in complement system genes alter an individual's risk of developing AMD. Recent studies have shown how some risk-associated genetic variants alter the function of the complement system. In this review, we describe the evolution of the complement system and bring together recent research to form a picture of how changes in complement system genes and proteins affect the function of the complement cascade, and how this affects the development of AMD. We discuss the application of this knowledge to prevention and possible future treatments of AMD.

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Complement evasion of pathogens: Common strategies are shared by diverse organisms

Cited by 154 publications

References 49 publications

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

Structure of Factor H-binding Protein B (FhbB) of the Periopathogen, Treponema denticola

Complement in age-related macular degeneration: a focus on function

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