Interleukin-1 and host control of pulmonary histoplasmosis.

Abstract

We found that interleukin (IL)-1beta levels were elevated in the lungs of mice infected with Histoplasma capsulatum. Hence, we examined the influence that IL-1beta and IL-1 signaling has on host defenses against pulmonary histoplasmosis. In IL-1 receptor 1 knockout (IL-1R(-/-)) mice challenged intratracheally, fungal recovery on day 7 after infection exceeded that in wild-type (WT) mice. Antibody neutralization of IL-1beta also exacerbated infection. For both groups of mice, the absence of bioactive cytokine led to a failure to control infection in a high proportion of mice. The absence of signaling had a modest effect on host resistance in mice with secondary histoplasmosis. Several perturbations in host defense mechanisms were detected in the lungs of IL-1R(-/-) mice. The number of CD4+ cells was decreased, and transcription of the gene for inducible nitric oxide synthase was depressed transiently. IL-4 and IL-10 levels were elevated in the lungs of IL-1R(-/-) mice, compared with those in the lungs of WT mice. Conversely, interferon- gamma levels were decreased. Thus, IL-1 contributes to host resistance to infection with H. capsulatum.