Childhood asthma is strongly associated with the development of atopy and T helper type 2 (Th2)-driven allergic airway inflammation

Childhood asthma is strongly associated with the development of atopy and T helper type 2 (Th2)-driven allergic airway inflammation (Sly et al., 2008; Holt and Sly, 2012). However, the mechanisms involved in the induction of a Th2-biased immunologic response are poorly understood. Moreover, the cause-and-effect relationship between inflammation, airway remodeling and airway hyperresponsiveness (AHR), as well as the temporal sequence of development of these changes, remain incompletely defined. What is clear is that both genetic and environmental factors are crucial in the induction of asthma in children. Epidemiological studies have identified that important environmental triggers include early-life lower respiratory viral infection associated with wheezing (Sly et al., 2008; Holt et al., 2009) and exposure to environmental tobacco smoke (Gilmour et al., 2006; Wigle et al., 2008). More recently, a number of large population-based studies, including prospective cohort studies, have demonstrated a significantly increased risk of development of asthma in children exposed to traffic-related particulate pollutants (Gehring et al., 2010; McConnell et al., 2010; Pénard-Morand et al., 2010). Such studies also indicate that, in the past, the burden of exacerbations of asthma among children whose asthma was caused by living near roadways might have been significantly underestimated (Perez et al., 2012). Thus, the adverse respiratory effects of exposure to ambient pollutants, notably diesel exhaust particulates, are increasingly being recognized as a global public health problem of mounting significance (Laumbach and Kipen, 2012). However, the design of appropriate control strategies is hindered by the lack of knowledge about specific mechanisms (Balmes, 2011). This lack of knowledge is related, at least in part, to the paucity of studies using appropriate experimental models. In particular, there have been few reports involving exposure of neonatal or weanling animals to these environmental triggers in the context of exposure to a sensitizing antigen via the respiratory tract and ongoing antigenic challenge, which is the context in which childhood asthma develops. We recently described a model of the induction phase of childhood asthma following early-life viral infection, involving a self-limiting infection with a murine pneumovirus followed by recurrent inhalational challenge with antigen (Siegle et al., 2010). Using this model, we demonstrated that development of airway inflammation typical of mild asthma, with a Th2-biased immunologic response and recruitment of