Mannose-binding lectin complement pathway plays a key role in complement activation by Paracoccidioides brasiliensis

Abstract

Paracoccidioides brasiliensis (Pb) is a dimorphic fungal pathogen that causes paracoccidioidomycosis the most severe deep mycosis from South America Although cell mediated immunity is considered the most efficient protective mechanism against Pb infection mechanisms of innate immunity are poorly defined Herein we investigated the interaction of the complement system with high and low virulence isolates of Pb We demonstrated that Pb18 a high virulence Pb Isolate when incubated with normal human serum (NHS) induces consumption of hemolytic complement and when immobilized promotes binding of C4b C3b and C5b-C9 Both low virulence (Pb265) and high virulence (Pb18) isolates consumed C4 C3 and mannose-binding learn (MBL) of MBL-sufficient but not of MBL-deficient serum as revealed by deposition of residual C4 C3 and MBL on immune complexes and mannan However higher complement components consumption was observed with Pb265 as compared with Pb18 The suggested relationship between low virulence and significant complement activation properties of Pb isolates was confirmed by the demonstration that virulence attenuation of Pb 18 results in acquisition of the ability to activate complement Conversely reactivation of attenuated Pb18 results in loss of the ability to activate complement Our results demonstrate for the first time that Pb yeasts activate the complement system by the lectin pathway and there is an Inverse correlation between complement activating ability and Pb virulence These differences could exert an influence on Innate immunity and severity of the disease developed by infected hosts (C) 2010 Elsevier Ltd All rights reserved