Similarly, in bind FH through expression of M proteins. attack by accelerating decay of convertases and by helping to inactivate C3 fragments on host cells. Pathogens, most of which do not have polyanionic markers, are not recognized by FH. Numerous pathogens, including certain bacteria, viruses, protozoa, helminths, and fungi, can recruit FH to protect themselves against host-mediated match attack, using either specific receptors and/or molecular mimicry to appear more like a host cell. This review will explore pathogen match evasion mechanisms including FH recruitment Rabbit Polyclonal to SUPT16H with an emphasis on: (a) characterizing the structural properties and expression patterns of pathogen FH binding proteins, as well as other strategies used by pathogens to capture FH; (b) classifying domains of FH important in pathogen conversation; and (c) discussing existing and potential treatment strategies that target FH interactions with pathogens. Overall, many pathogens use FH to avoid match attack and appreciating the commonalities across these diverse microorganisms deepens the understanding of match in microbiology. Keywords: match system, alternate pathway, Factor H, Factor H binding proteins, match evasion, pathogen The Match System Match activates through a domino-like cascade comprising over 50 proteins, resulting in outcomes essential for innate and adaptive immunity. Activation of match occurs through three pathways: classical, lectin, and alternate (Physique 1A), which converge around the cleavage of the central component, C3 [examined in (1)]. The classical pathway (CP) activates when C1q of the C1 complex (C1q, C1r, C1s) recognizes and binds pathogen- or cell-bound immunoglobulins, circulating immune complexes, or to pentraxins (e.g., C-reactive protein, pentraxin 3, serum amyloid P). When C1q binds a ligand, C1r is usually activated, which then activates C1s. C1s sequentially cleaves C4 and C2, resulting in the CP C3 convertase, C4bC2b [examined in (2)]. The lectin pathway (LP) activates when mannose-binding lectin (MBL), ficolins, or collectins identify molecular Cefsulodin sodium patterns such as carbohydrates and other ligands on foreign surfaces. This prospects to activation of MBL-associated serine proteases (MASPs), whereby MASP-2 cleaves C4 and C2 to form the LP C3 convertase, C4bC2b [examined in (3)]. Cefsulodin sodium Open in a separate windows Physique 1 Overview and regulation of the match system. (A) Complement is usually activated Cefsulodin sodium by three pathways: the classical, lectin, and option pathways. The classical pathway (CP) activates when the C1 complex (C1q, C1r, C1s) recognizes and binds pathogen- or cell-bound immunoglobulins, circulating immune complexes, or pentraxins. The lectin pathway (LP) activates when mannose-binding lectin (MBL) ficolins, or collectins identify molecular patterns such as carbohydrates and other ligands on foreign surfaces. CP and LP activation results in cleavage of C4, followed by cleavage of C2, forming the CP/LP surface bound C3 convertase, C4bC2b. The alternative pathway (AP) is usually spontaneously activated when soluble C3 hydrolyzes to C3(H2O). C3(H2O) can bind FB (labeled B) and recruit Factor D (labeled D) which cleaves FB to Bb (and Ba), resulting in the fluid phase AP C3 convertase, C3(H2O)Bb. C3(H2O)Bb cleaves C3 to C3a and C3b. C3b then binds covalently to nearby surfaces to form membrane-bound C3 convertase, C3bBb. C3 convertases derived from all pathways cleave C3 to C3a and C3b. C3b combines with created C3 convertases to form the CP/LP C5 convertase (C4bC2bC3b) and AP C5 convertase (C3bBbC3bn). C5 is usually cleaved by C5 Cefsulodin sodium convertases to initiate the common, terminal pathway, which culminates in the formation of the membrane attack complex (MAC). C3b produced from the cleavage of C3 by.