Priming with Inhaled Antigen: the Role of CCR2 (B106)

Abstract

Abstract We have developed a murine asthma model in which inhalation of OVA and low levels of LPS results in a Th2 response via a TLR4 dependent mechanism. Unlike asthma models that initiate a response via an intra-peritoneal injection of OVA and alum, our model uses a natural route of exposure and therefore provides insight into how pulmonary Th2 responses are initiated. Asthmatic responses that involve priming via an intra-peritoneal injection of OVA and alum are reported to be CCR2 independent. In contrast, in our model CCR2−/− mice show reduced airway inflammation and antigen specific antibody production. It is known that CCR2−/− mice have decreased recruitment of monocytes to sites of inflammation. In addition, it is known that under inflammatory circumstances CCR2+ monocytes can mature into tissue dendritic cells. In our asthma model, we find that inhalation of OVA and LPS induces recruitment of dendritic cells into the lung. We are currently determining if these recruited dendritic cells contribute to initiation of an asthmatic response and if their absence is responsible for the decreased responses observed in CCR2 knockout mice.