krn-7000 and Candidiasis

Candida species are one major causal microorganism of hospital acquired bloodstream infections associated with high mortality. Phagocytes like neutrophils in innate immunity and CD4 T cells in acquired immunity have a major role in host defense immune response. It has been recently found that a type of innate-like lymphocyte called NKT cells respond against various organisms but its role in candidal infection remained unknown. Thus, we analyzed the role of NKT cells in the immune response against systemic candidiasis using mice deficient of NKT cells. In vivo studies revealed that invariant NKT cells play a limited role for controlling systemic candidal infection. On the other hand, studies looking at the role of glycolipid-activated NKT cells during candidal infection revealed that candida-infected mice injected with glycolipid had shorter survival period and greater number of fungal colonies in the kidney accompanied with reduced number of neutrophils in the blood and bone marrow. Surprisingly, glycolipid-mediated exacerbation of candidal infection was absent in IFNγ deficient mice. Co-infection of candida with intestinal commensals caused exacerbated infection in which IFNγ played a critical role in impairing fungal elimination. These results suggest that the excessive IFNγ released from candida and bacterial co-infection is a critical factor in worsening candidal infection.

Topics: Animals; Candidiasis; Coinfection; Disease Models, Animal; Disease Progression; Galactosylceramides; Humans; Immunity, Innate; Interferon-gamma; Intestines; Kidney; Leukocyte Count; Lymphocyte Activation; Mice; Microbial Interactions; Natural Killer T-Cells; Neutrophils