UC San Diego

Veterans returning from deployment in the Middle East have displayed chronic asthmatic-like symptoms after exposure to burn pits and sandstorms. These soldiers also encounter stressful environments during deployment, introducing another factor that could alter their immune response. In this thesis, we have investigated the impact of acute stress on lung inflammation in murine models, focusing on the role of innate lymphoid cells (ILCs) during exposure to the allergen Alternaria alternata (Alt) and burn pit constituents (BPCs) which include dioxins, hydrocarbons, and particulate matter. Our previous studies have shown that combinatory exposure to Alt and BPCs induces a mixed type 2 and non-type 2 inflammatory response, characterized by increased neutrophilia and a shift from ILC2 to ILC1-like populations. Single-cell RNA sequencing (scRNA-seq) of lung samples showed upregulation of neutrophilia-associated genes and stress-related genes in ILCs from Alt+BPC-challenged mice, indicating that stress exacerbates inflammatory responses. Here, we present a novel model to reflect an acute stress event followed by inhalation of BPCs or Alt focusing on analysis of lung granulocytes and innate lymphoid cells. Results indicated a significant decrease in different ILC subpopulations of stressed mice after either allergen or BPC exposure. This decline reflects reduced neutrophilia in non-type 2 inflammation and trending decreases in eosinophilia in type 2 inflammation. This study concludes that acute stress alters the immune response to lung inflammation. These findings suggest that stress, combined with BPC exposure, might contribute to the respiratory issues observed in exposed military personnel.