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Histoplasma capsulatum is a prevalent fungal pathogen in the United States, infecting approximately 500,000 individuals each year. Host protection requires an intact cell-mediated immune response. In this review, we will discuss how cytokines and chemokines influence protective immunity in H. capsulatum infection.
CCR5 is a chemotactic mediator for inflammatory cells as well as regulatory T cells (Tregs). In this study, we investigated the role of CCR5 during infection with the fungal pathogen Histoplasma capsulatum. Mice lacking CCR5 or treated with an mAb to CCL4 had impaired infiltration of inflammatory cells to the lungs. Despite displaying an elevated fungal… (More)
CCR5 is a potent mediator of regulatory T cell (Treg) chemotaxis. In murine histoplasmosis, mice lacking CCR5 or endogenous CCL4 have a reduced number of Tregs in the lungs, which results in accelerated resolution of infection. In this study, we demonstrate that CCR5 controls the outcome of Histoplasma capsulatum infection by dictating thymic and lymph node… (More)
Interleukin (IL)-4 subverts protective immunity to multiple intracellular pathogens, including the fungus Histoplasma capsulatum. Previously, we reported that H. capsulatum-challenged CCR2(-/-) mice manifest elevated pulmonary fungal burden owing to exaggerated IL-4. Paradoxical to our anticipation in IL-33 driving IL-4, we discovered that the latter… (More)
Influenza A virus (IAV) is an airborne pathogen that causes significant morbidity and mortality each year. Macrophages (Mϕ) are the first immune population to encounter IAV virions in the lungs and are required to control infection. In the present study, we explored the mechanism by which cytokine signaling regulates the phenotype and function of Mϕ via… (More)
In murine histoplasmosis, tumor necrosis factor α (TNF-α) antagonism increases the number of regulatory T cells (Tregs) in lungs, and these cells profoundly hinder protective immunity. Because CCR5 mediates Treg homing and proliferation, we determined the outcome of antagonizing TNF-α in CCR5(-/)(-) mice infected with Histoplasma capsulatum. The absence of… (More)
It is well established that the cytokine IL-12 and the transcription factor STAT4, an essential part of the IL-12 signaling pathway, are critical components of the Th1 differentiation process in T cells. In response to pathogenic stimuli, this process causes T cells to proliferate rapidly and secrete high amounts of the cytokine IFN-γ, leading to the Th1… (More)