Abstracts (complete list) - Wissenschaft Online

Kathrin Held, Elke Dauber, Michael Loos, Franz Petry
Susceptibility of complement deficient mouse strains to
systemic infection with Candida albicans
C. albicans can activate all three pathways of the complement system leading to
opsonization of the yeast cells, enhanced complement receptor mediated phagocytosis
and infiltration of neutrophils due to C5a chemotactic activity. The aim of this study was
to investigate the susceptibility to C. albicans infection in different complement deficient
mouse strains. We compared mice with targeted disruption of the C1qa gene (C1q-/-)
and a double knockout strain that lacks factor B and C2 (Bf/C2-/-). Mice were infected i.
p. with 10 8 yeast cells of C. albicans SC5314 and monitored for mortality. Bf/C2-/- mice
showed high mortality (90%) within the study period of 4 weeks. In contrast, mortality
in C1q-/- mice was below 20% and all C57BL/6 control mice survived. Preliminary
analysis of MBL-A and MBL-C double knockout mice suggest that they are more
susceptible to infection than C1qa-/- mice but definitely more resistant than Bf/C2-/-
mice. Kidneys of deceased mice were homogenized and the yeast load was estimated
by culture. C.f.u. counts were approximately one log higher in Bf/C2-/- mice compared
to C1qa-/- mice. PAS staining of kidney sections of Bf/C2-/- mice showed widespread
germ tube formation confirming the high c.f.u. counts from cultured tissue
homogenates. In C1qa-/- and MBL-A/C-/- mice germ tube formation was limited in size
and number. In vitro binding studies demonstrated low efficiency of C1q binding but
substantial binding of MBL-A and MBL-C. These results support the idea that total lack
of complement activation in Bf/C2 double knock-out mice leads to uncontrolled tissue
infection. Deficiency of classical pathway activation has only a low impact on host
defence against C. albicans whereas the lectin pathway might contribute to the host
defence against candidosis.