Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma

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Abstract
Summary: Background It has been proposed that T helper (Th)2‐driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter‐regulation can protect against allergic asthma.Objective To test whether Th1‐inducing infection with Bordetella pertussis protects against allergic asthma using well‐characterized murine models.Methods Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well‐characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function.Results We demonstrate that OVA sensitization does not affect the development of B. pertussis‐specific immune responses dominated by IgG2a and IFN‐γ and does not impair Th1‐mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA‐specific IgE. The pattern of cytokine responses, in particular OVA‐specific IL‐5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL‐10 and IL‐13 levels were enhanced in OVA‐stimulated spleen cell cultures and in lavage fluid from infected co‐sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper‐reactivity to methacholine exposure.Conclusion Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper‐reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators.

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