Abstract
SUMMARYCandida albicans systemic dissemination in immunocompromised patients is thought to develop from initial gastrointestinal (GI) colonisation. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but studies in mice have indicated that both neutropenia and GI mucosal damage are crucial for allowing widespread invasive C. albicans disease. Mouse models, however, provide limited applicability to genome-wide screens for pathogen or host factors – factors that might influence systemic dissemination following GI colonisation. For this reason we developed a Drosophila model to study intestinal infection by Candida. We found that commensal flora aided host survival following GI infection. Candida provoked extensive JNK-mediated death of gut cells and induced antimicrobial peptide expression in the fat body. From the side of the host, nitric oxide and blood cells influenced systemic antimicrobial responses. The secretion of SAP4 and SAP6 (secreted aspartyl proteases) from Candida was also essential for activating systemic Toll-dependent immunity.
Highlights
Over the past decade the incidence of invasive fungal infection in immunocompromised individuals has dramatically increased, with candidiasis being the most common (Mèan et al, 2008)
The number of wild-type larvae developing to adults was significantly lower than when the parental strain was not grown in GF conditions (58%) and that of dif, key mutants was dramatically reduced to 22% (Fig. 1A)
These data indicated that indigenous bacterial flora acted antagonistically towards Candida, because as soon as they were removed the effect of Candida on host survival was much more pronounced
Summary
Over the past decade the incidence of invasive fungal infection in immunocompromised individuals has dramatically increased, with candidiasis (candidosis) being the most common (Mèan et al, 2008). Three mechanisms promote pathogenic fungal translocation: (1) disruption of the equilibrium in GI flora, thereby permitting intestinal overgrowth of pathogens; (2) increased permeability of the intestinal mucosal barrier; and (3) deficiencies in host defences (Shoham and Levitz, 2005). The majority of those models, have employed administration of a chemotherapeutic agent (e.g. cyclophosphamide) followed by the subsequent intravenous injection of C. albicans (Andes et al, 2003; Coligan, 2001). A mouse model that first establishes GI colonisation followed by Received 27 August 2010; Accepted 10 March 2011
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