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Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection.
Kennedy, Alexander T; Schmidt, Christoph Q; Thompson, Jennifer K; Weiss, Greta E; Taechalertpaisarn, Tana; Gilson, Paul R; Barlow, Paul N; Crabb, Brendan S; Cowman, Alan F; Tham, Wai-Hong.
Afiliación
  • Kennedy AT; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia;
  • Schmidt CQ; Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, 89081 Ulm, Germany;
  • Thompson JK; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;
  • Weiss GE; Burnet Institute, Melbourne, Victoria 3004, Australia;
  • Taechalertpaisarn T; Burnet Institute, Melbourne, Victoria 3004, Australia;
  • Gilson PR; Burnet Institute, Melbourne, Victoria 3004, Australia; Department of Immunology, Monash University, Victoria 3004, Australia;
  • Barlow PN; School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, United Kingdom; School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom; and.
  • Crabb BS; Burnet Institute, Melbourne, Victoria 3004, Australia; Department of Immunology, Monash University, Victoria 3004, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
  • Cowman AF; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia;
  • Tham WH; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia; tham@wehi.edu.au.
J Immunol ; 196(3): 1239-48, 2016 Feb 01.
Article en En | MEDLINE | ID: mdl-26700768
The human complement system is the frontline defense mechanism against invading pathogens. The coexistence of humans and microbes throughout evolution has produced ingenious molecular mechanisms by which microorganisms escape complement attack. A common evasion strategy used by diverse pathogens is the hijacking of soluble human complement regulators to their surfaces to afford protection from complement activation. One such host regulator is factor H (FH), which acts as a negative regulator of complement to protect host tissues from aberrant complement activation. In this report, we show that Plasmodium falciparum merozoites, the invasive form of the malaria parasites, actively recruit FH and its alternative spliced form FH-like protein 1 when exposed to human serum. We have mapped the binding site in FH that recognizes merozoites and identified Pf92, a member of the six-cysteine family of Plasmodium surface proteins, as its direct interaction partner. When bound to merozoites, FH retains cofactor activity, a key function that allows it to downregulate the alternative pathway of complement. In P. falciparum parasites that lack Pf92, we observed changes in the pattern of C3b cleavage that are consistent with decreased regulation of complement activation. These results also show that recruitment of FH affords P. falciparum merozoites protection from complement-mediated lysis. Our study provides new insights on mechanisms of immune evasion of malaria parasites and highlights the important function of surface coat proteins in the interplay between complement regulation and successful infection of the host.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malaria Falciparum / Factor H de Complemento / Activación de Complemento / Evasión Inmune Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Immunol Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malaria Falciparum / Factor H de Complemento / Activación de Complemento / Evasión Inmune Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Immunol Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos