Increased susceptibility of complement factor B/C2 double knockout mice and mannan-binding lectin knockout mice to systemic infection with Candida albicans.

Candida albicans is the major cause of systemic fungal infections in immunocompromised patients. We investigated the susceptibility of mice deficient in complement factor B and C2 (Bf/C2-/-), C1q (C1qa-/-), and mannan-binding lectin (MBL)-A (MBL-A) and MBL-C (MBL-A/C-/-) to systemic infection with C. albicans. Animals were infected i.p. with 10(8)C. albicans blastoconidia and monitored for mortality. Bf/C2-/- mice showed high mortality (over 90%) within the study period of 3 weeks. In contrast, mortality in C1qa-/- mice was below 15% whereas that of MBL-A/C-/- mice was 40% (P<0.001). Intravenous infection of mice with 8x10(5) blastoconidia resulted in the same trend with Bf/C2-/- mice being highly susceptible compared to the other strains. Histology of kidney sections of infected Bf/C2-/- mice showed widespread mycelia confirming the high CFU counts from cultured tissue homogenates. In C1qa-/-, MBL-A/C-/- and wild type C57BL/6 mice hyphal growth was limited. However, massive inflammatory infiltration was apparent, which was not seen in Bf/C2-/- mice. The ability of the mouse sera to opsonize C. albicans was determined by quantification of phagocytosis of C. albicans by peritoneal phagocytes. Whilst phagocytosis mediated by Bf/C2-/- mouse serum was low (10.6%), more phagocytosis could be seen in MBL-A/C-/- (19.9%), C1qa-/- mice (23.9%) and wild type mice (29%). Deficiency of classical pathway activation has only a low impact whereas the lectin pathway contributes to the host defence against candidosis. The more pronounced lack of complement activation in Bf/C2-/- mice leads to uncontrolled infection due to an opsonophagocytic defect.

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