Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 10, Pages 2875-2885Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI25365
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI-42747, AI-34361, R37 AI042747, R01 AI034361] Funding Source: Medline
Ask authors/readers for more resources
Pathogen-induced apoptosis of lymphocytes is associated with increased susceptibility to infection. In this study, we determined whether apoptosis influenced host resistance to the fungus Histoplasma capsulatum. The level of apoptotic leukocytes progressively increased in the lungs of naive and immune mice during the course of H.capsulatum infection. T cells constituted the dominant apoptotic population. Apoptosis was diminished in H.capsulatum-infected gld/gld and TNF-alpha-deficient mice; concomitantly, the fungal burden exceeded that of controls. Treatment of naive and H.capsulatum-immune mice with caspase inhibitors decreased apoptosis but markedly enhanced the severity of infection. Administration of a proapoptotic: dose of suramin diminished the fungal burden. The increased burden in recipients of a caspase inhibitor was associated with elevations in IL-4 and IL-10 levels. In the absence of either of these cytokines, caspase inhibition suppressed apoptosis but did not increase the fungal burden. Thus, apoptosis is a critical element of protective immunity to H. capsulatum. Production of IL-4 and IL-10 is markedly elevated when apoptosis is inhibited, and the release of these cytokines exacerbates the severity of infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available