PMC:4503824 / 12990-14597 JSONTXT

{"project":"2_test","denotations":[{"id":"25498576-1831795-43267776","span":{"begin":745,"end":749},"obj":"1831795"},{"id":"25498576-21723612-43267776","span":{"begin":745,"end":749},"obj":"21723612"},{"id":"25498576-16714537-43267777","span":{"begin":1129,"end":1133},"obj":"16714537"},{"id":"25498576-12884862-43267777","span":{"begin":1129,"end":1133},"obj":"12884862"},{"id":"25498576-24789368-43267778","span":{"begin":1426,"end":1430},"obj":"24789368"},{"id":"25498576-7216421-43267779","span":{"begin":1601,"end":1605},"obj":"7216421"}],"text":"Similarly to Fc mediated uptake, complement binds to a heterodimer of integrin receptors (CR3; CD11b/CD18) and activates actin mediated phagocytosis. The complement cascade completes three key roles during pathogen infection: Opsonisation, direct killing of pathogens and recruitment of inflammatory cells. The complement cascade converges with the production of C3 convertase, and subsequent creation of C3b, via three main pathways; classical, lectin and alternative, which in turn lead to production of C5a and C5b. The alternative pathway mediates the role of complement protein in host defence against C. neoformans, although nonencapsulated cryptococci are able to activate the classical pathway (Kozel et al., 1991; Mershon-Shier et al., 2011). Cryptococcal capsule accumulates C3 via the alternative pathway and deposition of C3 near the surface is needed for efficient phagocytosis. However, if C3 is evenly distributed throughout the capsule increased volume of capsular polysaccharide will reduce the amount on the surface resulting in reduced complement mediated phagocytosis (Gates and Kozel, 2006; Zaragoza et al., 2003). To add to this, recently a cryptococcal hydrolytic enzyme, lactonohydrolase (LHC1), was shown to combat the complement cascade through inducing capsular changes which reduces C3 deposition on the capsule, a lhc1 mutant that had increased C3 deposition and decreased virulence (Park et al., 2014). Another complement protein, C5 is also implicated, with mice strains more susceptible to cryptococcal infection when C5 was not present in their plasma (Rhodes et al., 1980)."}