Iron Overload Alters Innate and T Helper Cell Responses to Candida albicans in Mice

The effect of iron overload on susceptibility of mice to Candida albicans infection and on the type of T helper (Th) immunity elicited was investigated. Iron overload greatly increased susceptibility to disseminated infection with low-virulence C. albicans cells of exogenous origin. The candidacidal activity and the ability to release nitric oxide and bioactive interleukin (IL)-12 were greatly impaired in neutrophils and macrophages from infected mice. CD4 T cells from spleens of iron-overloaded mice were found to produce high levels of IL-4 and IL-10 and low levels of interferon-g. Treatment of iron-overloaded mice with the iron chelator, deferoxamine, resulted in the cure of mice from infection, restored the antifungal effector and immunomodulatory functions of the phagocytic cells, and allowed the occurrence of CD4 Th1 protective antifungal responses. These data indicate that iron overload may negatively affect CD4 Th1 development in mice with candidiasis, a function efficiently restored by therapy with deferoxamine. Helper T (Th) cells play a central role in regulating immune responses in mice with candidiasis [1]. A defective innate imresponses to the fungus Candida albicans by secreting cyto- mune response also contributes to the inability of interleukin kines that modulate the development and activity of immune (IL)-6 ‐ deficient mice to mount protective Th1 responses in effectors. The dominance of either of the Th subsets (Th1 infection with C. albicans [10]. These results indicate that and Th2) correlates directly with the outcome and severity of phagocytic cells could act not only as effectors but also as infection [1, 2]. In experimental models of candidiasis, protec- regulators of cell-mediated immunity in mice with candidiasis. tion correlates with polarization toward the Th1 differentiation Such a finding, while evidencing the complexity of the interdepathway, as observed in genetically resistant mice injected with pendence among the different types of immunity [11], also a live vaccine strain of the yeast or in susceptible mice injected suggests that factors affecting the efficiency of the innate imwith virulent C. albicans cells, provided that the Th2 cytokines mune system may have an impact on the subsequent anticandiare neutralized [3 ‐ 5]. In contrast, Th2 responses are associated dal Th cell development. with disease exacerbation and pathology [6 ‐ 8].