LPS-INDUCED MACROPHAGE (M??) ACTIVATION AUGMENTS PHAGOCYTOSIS OF CANDIDA GLABRATA

Abstract

Candida glabrata is now the 2nd or 3rd most frequent cause of candidemia (after C. albicans) in trauma patients, but little is known about its pathogenesis. Others have reported that systemic injection with Escherichia coli (or its LPS) augments systemic C. albicans infection, but the opposite may be true for C. glabrata. Fourteen days after 108 intravenous C. glabrata, mice were injected intraperitoneally (ip) with 108E. coli (live or heat-killed), 100 μg E. coli LPS, or saline, and sacrificed 16 hr later. Numbers of C. glabrata recovered from the kidneys were consistently decreased in mice given E. coli or its LPS.TableTo clarify the role of LPS-induced MØ activation in clearance of C. glabrata, glass-adherent mouse peritoneal exudate cells (>90% positive for the F4/80 MØ antigen) were incubated with 0 or 100 μg/ml LPS for 24 hr, with MØ activation confirmed by increased fluorescent intensity to rat-anti-mouse MARCO (MØ receptor with collagenous structure) antibody (687 versus 2664 fluorescent intensity units, Metamorph software, P < 0.01, t-test). After 30 min incubation with 106C. glabrata, LPS-activated MØs had increased numbers of cell-associated C. glabrata, measured by light microscopy of Wright-Giemsa stained cultures (avg of 6.4 versus 3.7 C. glabrata per MØ incubated with and without LPS, P < 0.01, t-test, three experiments containing observations from 450 MØs). Thus, LPS-induced MØ activation was associated with a nearly 2-fold increase in C. glabrata phagocytosis. These data indicate that clinical conditions, or therapeutic agents, that increase MØ activation may help ameliorate systemic infection with C. glabrata.