Single cell RNASeq analysis of memory TH2 cell response to an intestianl nematode

Intestinal parasitic nematodes, affecting a quarter of the world’s population, typically elicit prominent effector Th2-driven host immune responses. However, a more detailed understanding of nematode-induced memory Th2 responses remains scarce. We investigated the activation of peritoneal memory Th2 cells and the mechanisms driving early recall responses to the enteric nematode Heligmosomoides polygyrus in mice. We show memory Th2 cells with distinct transcriptional profiles to persist systemically in lymphoid and non-lymphoid tissues following cure of infection. Moreover, peritoneal memory Th2 cells display strong cytokine production, upregulate costimulatory marker Ox40 (CD134) and IL-5 production in a parasite-specific manner as early as 3 days following challenge infection. This effect is paralleled by an influx of Ox40L+ dendritic cells (DC) and eosinophils, both appearing exclusively in the peritoneum of reinfected mice. Finally, we show that peritoneal mesothelial cells (PeM) significantly downregulate their expression of VCAM-1 and ICAM-1 in response to a secondary infection, pointing towards an involvement in immune cell efflux. Thus, our data indicate a pivotal role of the peritoneum for memory Th2 responses and a role for PeM cells in immune cell recruitment, activation and efflux during recall responses to a strictly intestinal pathogen. RNA from single TH2 cells derived from different tissues of two mice cured after nematode infection