Alternaria aerosol during a bovine respiratory syncytial virus infection alters the severity of subsequent re-infection and enhances IgE production

Background: Previous studies with cattle and rodent models have shown that bovine and human RSV infections influence the immune response to inhaled allergen. In the present study, we extended these observations to examine the effect of fungal allergen Alternaria alternata aerosol exposure (prior to and during BRSV infection) on the immune response and clinical outcome of a secondary BRSV infection. Methods: Calves were either Alternaria (Alt)/mock Alt (mAlt) and BRSV/mBRSV exposed. Exposures began on day -6 and continued every other day until day 6 post infection. A second set of aerosols/infection began on day 103 and continued as before. Clinical outcome during infections was measured in each group. IgG1, IgA, and IgE responses to Alternaria were measured in serum or bronchiolar alveolar lavage fluid (BALF). Cytokine responses, including IL-4, were also measured. Results: Alternaria did not influence primary infection; however, the Alt/BRSV group had less disease than mAlt/BRSV group (median clinical score 8 vs 476.5; p≤0.01) after secondary infection. Exposure to Alternaria facilitated IgE antibody production in BRSV infected calves. IgE responses to Alternaria were higher in Alt/BRSV than Alt/mBRSV animals on day 10 (mean baseline fold increase 1.97 vs 1.06; p=0.013) and 109 (1.40 vs 0.810; p=0.008). Comparatively, Alt/BRSV calves had less Alternaria specific IgG1 than Alt/mBRSV calves on days 0, 107, 109, 113, 115, and 120 (p≤0.05) with more lung eosinophils and IL-4 secreting PBMCs. Conclusion: Alternaria aerosols during primary and secondary BRSV infections decreased disease in secondary infections; however, BRSV infection enhanced Th2 responses against inhaled Alternaria.