Interleukin-1 and host control of pulmonary histoplasmosis.
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.
Deepe
George S
GS
Cincinnati Veterans Affairs Medical Center and Division of Infectious Diseases, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0560, USA. george.deepe@uc.edu
McGuinness
Michael
M
D000818:Animals; D000961:Antilymphocyte Serum / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D006658:Histoplasma; D006660:Histoplasmosis / Q000276:immunology*; D007375:Interleukin-1 / Q000032:analysis / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D013997:Time Factors
D000961:Antilymphocyte Serum; D016207:Cytokines; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D019001:Nitric Oxide Synthase