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

Abstract

SummaryBackground 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. pertussisspecific immune responses dominated by IgG2a and IFN-g 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.

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

“…2B). In contrast, a combination of immunization and infection prior to OVA sensitization (group PaBpOVA) resulted in a significant reduction in the OVA-specific IgE titer compared to that in mice sensitized to OVA in the absence or the presence of Pa immunization (groups OVA and PaOVA, respectively, for which P ϭ 0.0447 and 0.0413, respectively), similar to the effect previously reported (8) for infection in combination with OVA sensitization (group BpOVA) (Fig. 2B).…”

“…OVA sensitization induced high levels of OVA-specific IgE, as reported previously (8). Notably, Pa did not enhance the OVA-specific IgE response (Fig.…”

“…Female BALB/c (age, 6 to 8 weeks; Harlan, Bicester, Oxon, United Kingdom) mice were used under the guidelines of the Irish Department of Health and the research ethics committee of the National University of Ireland, Maynooth. The BALB/c strain was selected because the performance of pertussis vaccines in this strain has been shown to correlate well with the performance of the vaccines in clinical trials with humans (37) and allergic asthma in this strain has been shown to be consistent with previous models of allergic asthma (8).…”

“…We have previously shown that infection with B. pertussis modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma (8). Furthermore, we have demonstrated that Th1-inducing Pw protects against exacerbation of allergic asthma due to B. pertussis (7).…”

“…On the other hand, several studies have suggested that viral and bacterial infections exacerbate asthma. For example, respiratory syncytial virus, commonly associated with pulmonary infections in infancy, is known to exacerbate asthma (24,30), and recently, we have shown that Bordetella pertussis infection exacerbates allergic asthma in a murine ovalbumin (OVA) model (8).…”