Abstract
Early infection with Respiratory Syncytial Virus (RSV) has long been recognized to predispose certain individuals towards the development of asthma. The immune response to RSV is unique in that it consists of protective Th1 and immunopathologic Th2-type features. Though much is known about the pathology of this disease it is still unclear how RSV infection leads to asthma development. Thymic Stromal Lymphopoietin (TSLP) is a cytokine that has been shown to be both necessary and sufficient for the development of asthma. Mice that express a lung-specific TSLP transgene (SPC-TSLP) develop a spontaneous and progressive asthma-like disease while TSLPRKO mice are highly resistant to disease in an antigen-specific asthma model. In this study we highlight a possible role for TSLP as the link between RSV infection and asthma development. We demonstrate that TSLP overexpression results in sensitization and the development of allergy to environmental antigens. Further, we show for the first time that RSV and its relative, Sendai Virus, lead to increases in TSLP expression by airway epithelial cells both in vitro and in vivo. Taken together these data suggest that TSLP induced by RSV during primary infection may increase susceptibility or directly result in asthma development. Additionally, in this study we show that the RIG-I viral recognition pathway represents a novel pathway leading to TSLP expression.
