Parenchymal Organ, and Not Splenic, Immunity Correlates with Host Survival during Disseminated Candidiasis

Abstract

We examined the relationship between host survival and renal and splenic immune responses in a murine model of hematogenously disseminated candidiasis. Male BALB/c mice were infected via tail vein injection with wild-type C. albicans or with an isogenic, Δefg1/Δefg1 hypha-deficient mutant. Host survival, organ fungal burden, intracellular cytokine content of splenic and kidney lymphocytes, and whole-organ cytokine profiles were determined. Wild-type C. albicans induced type 2 splenocyte responses with both nonfatal and fatal inocula. In the kidney, conversely, wild-type inocula causing no or low mortality induced type 1 responses and 100% fatal inocula induced type 2 or interleukin-10 (IL-10)-dominant responses. Hypha-deficient mutant C. albicans caused no or low mortality while inducing type 1 responses in both the spleen and kidney. To our knowledge, this is the first demonstration that host survival during systemic infection correlates with the type of immune response engendered in a nonlymphoid, parenchymal organ and not with the response in the spleen. Furthermore, the results provide in vivo confirmation that hyphal formation by C. albicans induces type 2 or IL-10-dominant host responses in tissues.