Toll-like receptor 2 mediates prostaglandin E2 production in murine peritoneal macrophages and splenocytes in response to Candida albicans

The involvement of Toll-like receptor 2 (TLR2) and TLR4 in triggering signal transduction pathways leading to prostaglandin E2 (PGE2) production in response to Candida albicans has been studied in cells from wild-type, TLR2-/- and TLR4-/- knockout mice. In vitro PGE2 production by macrophages challenged with zymosan, yeast or hypha cells was strongly inhibited in TLR2-deficient cells, but not in TLR4-/- cells, as compared to macrophages from wild-type mice. PGE2 production was dependent on de novo cyclooxygenase-2 (Cox2) synthesis, since unchallenged cells failed to produce PGE2 and specific Cox2 inhibition during challenge totally blocked PGE2 production. Similar results were obtained following in vitro challenge of splenocytes from mice intravenously infected with the low-virulent C. albicans PCA2 strain. This indicates that TLR2 is the major receptor that mediates PGE2 production in response to C. albicans, probably by upregulating Cox2 expression.