Abstract
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.