Project description:Allergens such as house dust mites (HDM) and papain induce strong Th2 responses, including elevated IL-4, IL-5, and IL-13 and marked eosinophilia in the airways. Histoplasma capsulatum is a dimorphic fungal pathogen that induces a strong Th1 response marked by IFN-? and TNF-? production, leading to rapid clearance in nonimmunocompromised hosts. Th1 responses are generally dominant and overwhelm the Th2 response when stimuli for both are present, although there are instances when Th2 stimuli downregulate a Th1 response. We determined if the Th2 response to allergens prevents the host from mounting a Th1 response to H. capsulatum in vivo. C57BL/6 mice exposed to HDM or papain and infected with H. capsulatum exhibited a dominant Th2 response early, characterized by enhanced eosinophilia and elevated Th2 cytokines in lungs. These mice manifested exacerbated fungal burdens, suggesting that animals skewed toward a Th2 response by an allergen are less able to clear the H. capsulatum infection despite an intact Th1 response. In contrast, secondary infection is not exacerbated by allergen exposure, indicating that the memory response may suppress the Th2 response to HDM and quickly clear the infection. In conclusion, an in vivo skewing toward Th2 by allergens exacerbates fungal infection, even though there is a concurrent and unimpaired Th1 response to H. capsulatum.
Project description:Genome-wide reprogramming of transcript architecture by temperature specifies the developmental states of the human pathogen Histoplasma [ribosome profiling]
