Aeroallergens Exacerbate Histoplasma capsulatum Infection

Area of Science:

• Immunology
• Infectious Diseases
• Allergy Research

Background:

• Allergens like house dust mites (HDM) and papain trigger Th2 immune responses, characterized by specific cytokines and eosinophilia.
• The fungus *Histoplasma capsulatum* typically elicits a Th1 immune response, leading to pathogen clearance in healthy individuals.
• Generally, Th1 responses dominate over Th2 responses, but Th2 stimuli can sometimes suppress Th1 activity.

Purpose of the Study:

• To investigate whether a Th2 immune response induced by allergens hinders the host's ability to mount an effective Th1 response against *Histoplasma capsulatum* infection in vivo.
• To determine if allergen-induced Th2 skewing exacerbates fungal infections despite an active Th1 response.

Main Methods:

• C57BL/6 mice were exposed to allergens (HDM or papain) and subsequently infected with *Histoplasma capsulatum*.
• Immune responses, including Th1 and Th2 cytokine levels, eosinophil counts, and fungal burden, were assessed in the lungs.
• The impact of allergen exposure on primary and secondary fungal infections was evaluated.

Main Results:

• Mice exposed to allergens and infected with *H. capsulatum* displayed a dominant early Th2 response with increased eosinophilia and Th2 cytokines.
• These mice showed significantly higher fungal burdens, indicating impaired clearance of *H. capsulatum*.
• Secondary infection with *H. capsulatum* was not exacerbated in allergen-exposed mice, suggesting a role for immune memory.

Conclusions:

• In vivo skewing towards a Th2 immune response by allergens exacerbates fungal infections, even when a concurrent Th1 response remains intact.
• The findings suggest that allergen-induced Th2 dominance compromises the host's defense against *H. capsulatum*.
• Immune memory appears to mitigate the exacerbating effect of allergens on secondary fungal infections.