Parenchymal organ, and not splenic, immunity correlates with host survival during disseminated candidiasis.
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, Deltaefg1/Deltaefg1 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.
D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology; D015169:Colony Count, Microbial; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009928:Organ Specificity; D011379:Prognosis; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014774:Virulence
D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma