Early life stress increase LPS and Poly I:C mediated inflammatory response in adult males, but not females 3343

Description In children, stressful events or abuse disrupt the development of the immune response. While the long-term consequences of early life stress on the cortisol response are sex-specific, there is limited knowledge on the impacts of stress on development of the immune responses in males and females. To test the hypothesis that early life stress induces sex-specific alterations of lung immune response, we used a well-established rat model of early life stress: neonatal maternal separation (NMS; 3h/ day from post-natal days 3 to 12). Lung inflammatory responses to either Poly I:C or LPS were assessed in adult rats of both sexes that were subjected to NMS or control conditions; we characterized the innate and adaptive immune cell subsets from broncho-alveolar lavage (BAL) and lung tissue using flow cytometry. NMS increased total BAL cell accumulation after LPS exposure, especially in male NMS, whereas after Poly I:C exposure, there was lower cell recruitment, markedly in female NMS. Following LPS exposure, male NMS had an increased neutrophilic inflammation whereas female NMS had higher proportion of alveolar macrophages. In lungs, proportion of natural killer cells (NK) increased in male NMS whereas proportion of T cells CD4+ was higher in female NMS following Poly I:C exposure. These results indicate that inflammatory immune responses are altered by NMS in a sex-specific manner, even though corticosterone dysregulation after NMS is only observed in males. Funding Sources Funding: CIHR, FRQS, Quebec Respiratory Health Network and Fondation IUCPQ. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)