In the last 20 years more than 3 million United States military personnel have been deployed overseas and emerging evidence suggests that deployed personnel have a much greater risk of developing respiratory diseases such as asthma. Among Veterans Affairs patients who were deployed to Iraq and Afghanistan, asthma prevalence nearly tripled. Studies conducted by the Department of Defense analyzing military encounter data demonstrate increased encounters occur for respiratory symptoms, predominantly asthma, after deployment. One potential explanation is that U.S. military personnel deployed in Southwest Asia and Afghanistan experience elevated exposures to particulate matter (PM) and other inhalational exposures including desert dust and burn pit combustion. In particular deployed troops are exposed to diesel fuel which is extensively used in ground equipment and in many tracked and wheeled vehicles. Thus, understanding how inhalational exposures trigger allergic airway inflammation (AAI), whether this is exacerbation of existing disease or precipitation of de novo disease, is a critical need in military population. Allergen sensitized TH2 cells are required but not sufficient for the development of the allergic asthma phenotype. It is clear from the literature that not all allergic individuals develop asthma upon allergen exposure, despite systemic sensitization to airborne allergen. In this application we present compelling preliminary data that neutrophils promote pathogenic T cell response in the airway following inhalational challenge. Triggering Receptor Expressed on Myeloid Cell-1 (TREM-1), exclusively expressed on human neutrophils and monocytes, serves as a global regulator of immune responses. TREM-1 synergizes with Toll-like receptors, Nod-like receptors, and damage-associated molecular patterns to increase inflammation in response to inhalational exposures. We hypothesize that neutrophils modulate T cell responses to allergens in the airspace in a TREM-1 dependent manner. This hypothesis is built upon a growing body of literature that demonstrate that neutrophils have an important role in the pathogenesis of AAI and our strong Preliminary Data in TH2 dominant AAI. We demonstrate that neutrophils are present in high numbers immediately following allergen challenge in asthmatic subjects’ airways, that expression of neutrophil receptor TREM-1 exacerbates TH2 dominant AAI in vivo, and that neutrophils modulate T cell cytokine production in a TREM-1 dependent manner. In our Preliminary Data, we identify a novel TREM-1 dependent interaction between neutrophils and T cells that may shed light on the mechanism responsible for the large increase in AAI following exposure to airborne hazards in military populations. Using a TH2 dominant AAI model, Cre recombinase systems, and adoptive transfer, we will determine how TREM-1 promotes AAI severity as measured by airway hyperreactivity, cellular quantification by flow cytometry, cytokine levels, and h...