Aeroallergens Exacerbate Histoplasma capsulatum Infection

Abstract

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 (H. capsulatum) is a dimorphic fungal pathogen that induces a strong Th1 response marked by IFNγ and TNFα production, leading to rapid clearance in non-immunocompromised hosts. Th1 responses are generally dominant and overwhelm the Th2 response when stimuli for both are present, though 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 towards a Th2 response by an allergen are less able to clear the H. capsulatum infection despite an intact Th1 response. On the other hand, secondary infection is not exacerbated by allergen exposure, indicating the memory response may suppress the Th2 response to HDM and quickly clear the infection. In conclusion, an in vivo skewing towards Th2 by allergens exacerbates fungal infection, even though there is a concurrent and unimpaired Th1 response to H. capsulatum.

Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis

“…We used BALB/c mice to carry out long-term tissue inflammation that could mimic PF. They used to be classified as resistant to PF [ 27 , 28 ], but in several experimental lung infectious diseases, they develop chronic inflammation with fibrosis formation, as in the murine model of paracoccidioidomycosis [ 29 , 30 ] and histoplasmosis [ 31 , 32 ].…”