Low-dose streptozotocin-induced diabetes in mice. II. Susceptibility to Candida albicans infection correlates with the induction of a biased Th2-like antifungal response.
We have previously found that the development of fatal disseminated candidiasis correlates with the detection of a strong Th2 response, while protective antifungal immunity is associated with a predominant Th1 response. In the present study we verified the hypothesis that an altered antifungal Th response could be responsible for the high susceptibility of diabetic mice to systemic Candida albicans infection. Outbred CD1 mice rendered diabetic with multiple low doses of the pancreatic islet beta-cell toxic, streptozotocin, develop a fatal systemic infection when injected with low-virulence C. albicans cells. Progressive disease was found to be associated with the presence in the serum of IgA, IgE, and IgG1 Candida-reactive specific antibodies, absent footpad reactions, and elevated production in vitro of the Th2 cytokines IL-4, IL-6, and IL-10 but not the Th1 cytokine IFN-gamma. Both the Th2 and Th1 (IL-2 and IFN-gamma) cytokines were produced in vitro by CD4+ lymphocytes from noninfected diabetic mice that, in addition, showed a noticeable footpad reaction to Candida antigens. Thus, it appears that a perturbation in the anticandidal T helper responses resulting in the induction of a biased Th2-like antifungal response renders diabetic mice highly susceptible to systemic C. albicans infection.
Mencacci
A
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Romani
L
L
Mosci
P
P
Cenci
E
E
Tonnetti
L
L
Vecchiarelli
A
A
Bistoni
F
F
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans; D002177:Candidiasis / Q000150:complications / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D013311:Streptozocin; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000908:Antibodies, Fungal; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D013311:Streptozocin; D007371:Interferon-gamma