Department of Respiratory Virology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
The aim of our study was to investigate the influence of influenza A virus infection on the apoptosis of ovalbumin (OVA)-induced allergy and its immune response at different timings of antigen exposure in mice. Male Balb/c mice were sensitized, resensitized and challenged with OVA. Influenza A virus was inoculated 5 days before the final challenge. We determined airway hyperreactivity (AHR), IgE, histopathological lesions in airways, apoptotic markers and PKR expression of OVA allergic mice after influenza A virus infection. During active allergen-induced airway inflammation, downregulation of FasL and Fas receptor expression negatively modulates apoptosis, leading to persistent bronchial inflammation in allergic asthma. Again diminished caspase activity in the airways along with the concomitant inflammatory response 24 h after OVA challenge may signify facilitation of inflammatory cell accumulation. Considerably lower degree of DNA fragmentation as seen in acute and OVA phase groups could be possibly due to downregulation of Th1 by Th2 response. Further, PKR expression signifies the fact that viral dsRNA can induce activation of a host's anti-viral protein kinase (PKR) and activation of PKR by dsRNA leads to expression of Th2-type immune responses, which in turn may lead to the exacerbation of allergic asthma. Thus, lung and airway destruction/damage appears to be caused by increased epithelial and endothelial cell death or inhibition of apoptosis of inflammatory cells. Moreover, hypoexpression of apoptotic markers by pulmonary T cells, with subsequent impairment of apoptosis in acute phase, may be the molecular basis for the development and persistence of inflammatory infiltrate in the mucosa of the respiratory tract. It may be hypothesized that influenza virus induced in OVA allergic mice do not lead to marked apoptosis rather leads to cytolysis, resulting in enhanced airway inflammation and severe exacerbation of asthma.
