S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.

Pathologically swollen lymph nodes (LNs), or buboes, characterize Yersinia pestis infection, yet how they form and function is unknown. We report that colonization of the draining LN (dLN) occurred due to trafficking of infected dendritic cells and monocytes in temporally distinct waves in response to redundant chemotactic signals, including through CCR7, CCR2, and sphingosine-1-phospate (S1P) receptors. Retention of multiple subsets of phagocytes within peripheral LNs using the S1P receptor agonist FTY720 or S1P1-specific agonist SEW2871 increased survival, reduced colonization of downstream LNs, and limited progression to transmission-associated septicemic or pneumonic disease states. Conditional deletion of S1P1 in mononuclear phagocytes abolished node-to-node trafficking of infected cells. Thus, Y. pestis-orchestrated LN remodeling promoted its dissemination via host cells through the lymphatic system but can be blocked by prevention of leukocyte egress from DLNs. These findings define a novel trafficking route of mononuclear phagocytes and identify S1P as a therapeutic target during infection.

Why is concealment associated with health and wellbeing? An investigation of potential mechanisms.

RATIONALE: Many members of stigmatized groups face health and wellbeing deficits relative to their non-stigmatized peers. Ample evidence suggests that one method used by some members of stigmatized groups to manage the stigma they face-concealing their stigmatized identities-may contribute to these health and wellbeing disparities. However, precisely why concealment may contribute to these disparities is less clear. OBJECTIVE: The present work seeks to identify and distinguish between plausible explanations for why concealment may contribute to worse health and wellbeing. METHODS: In the present work, we explore a large number of plausible mechanisms that may explain why concealment is associated with worse health and wellbeing. In three studies (N = 2304) using cross-sectional (Studies 1 and 2) and longitudinal (Study 3) methods, participants were recruited from an online recruitment pool (Studies 1-3) and from an institutional recruitment pool (Study 2). Participants reported on their concealment, health and wellbeing, and constructs related to plausible explanations for the relationships between concealment and health and wellbeing. RESULTS: We find that concealment is associated with worse health and wellbeing, with generally small effect sizes. We further find that lower feelings of belonging, less social support, and lower self-esteem are the most plausible mechanisms for explaining why concealment is associated with worse health and wellbeing. When between- and within-subjects effects were distinguishable (i.e., Study 3), we observed only between-subjects relationships. CONCLUSION: Because people's choices to engage in self-protection through concealment should be respected, potential avenues for intervention to reduce minority health disparities may be more appropriately targeted at the mechanisms that account for why concealment may undermine health and wellbeing than at concealment itself. The present work makes strides towards identifying those mechanisms and thus towards addressing them.