The complement fitness factor H: role in human diseases and for immune escape of pathogens, like pneumococci.
Factor H is the central regulator of the alternative complement pathway and controls early activation of the complement cascade at the level of the C3 convertase. Mutations in the Factor H gene are associated with severe and diverse diseases including the rare renal disorders hemolytic uremic syndrome (HUS) and membranoproliferative glomerulonephritis (MPGN) also termed dense deposit disease (DDD), as well as the more frequent retinal disease age related macular degeneration (AMD). In addition, pathogenic microbes utilize host complement Factor H for immune evasion and these pathogens express specific surface receptors which bind host innate immune regulators. Sequence variations or mutations of one single gene, coding for the host regulator Factor H, form the basis for multiple, different disorders such as human renal and retinal diseases as well as infections. This association of Factor H but also of additional related complement components and regulators with the same diseases demonstrate an important role of complement, particularly of the alternative pathway, for tissue homeostasis. Disturbances of this central immune surveillance system lead to damage of autologous tissues and surfaces and result in autoimmune diseases. Remarkably, pathogenic microbes copy this mechanism of immune surveillance: they mimic the composition of host cell's, bind Factor H to their surface and engage acquired host Factor H for immune disguise.
Zipfel
Peter F
PF
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany. peter.zipfel@hki-jena.de
Hallström
Teresia
T
Hammerschmidt
Sven
S
Skerka
Christine
C
D017242:Complement Factor H / Q000502:physiology*; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D011008:Pneumococcal Infections / Q000209:etiology* / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
D017242:Complement Factor H