Publication Database

The peritoneal cavity supports an early memory Th2 cell-driven recall response to challenge nematode infection (2021)

Art

Vortrag

Autoren

Yordanova, Ivet Antoni (WE 6)

Jürchott, Karsten

Steinfelder, Svenja

Sawitzki, Birgit

Hartmann, Susanne (WE 6)

Kongress

29th Annual Meeting of the German Society for Parasitology

digital, 15. – 17.03.2021

Quelle

Sprache

Englisch

Verweise

URL (Volltext): https://programm.conventus.de/index.php?id=dgp2021&tx_coprogramm_programm%5Bprogramm%5D=77&tx_coprogramm_programm%5Bsession%5D=14&tx_coprogramm_programm%5BcurrentPage%5D=&tx_coprogramm_programm%5Baction%5D=programm&tx_coprogramm_programm%5Bcontroller%5D=Source&cHash=2ce80925457fd1f91dcec5c0475f0aec

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Helminth infections induce strong host adaptive immune responses, driven by Gata3+CD4+ Th2 cells, IgG and IgE antibody production and eosinophilia. During chronicity, Th2 responses exhibit a functional downregulation, coinciding with elevated frequencies of regulatory T cells (Treg) and suppressive macrophages. In humans, helminth re-infections remain common, highlighting the absence of functional protective immunological memory. Nevertheless, the development of memory T cell responses to parasitic helminths is well documented in mice. Tissue-resident CD4+ memory T cells (TRM) represent a recently-described subset, which is preferentially induced locally at sites of pathogen encounter. These cells reside long-term within tissues, where they can rapidly and effectively respond upon re-infection.

Previously, we could show that non-lymphoid organs serve as reservoir for functional resident memory CD4+ T cells(1). Here, we aimed to further study the circuits of activation and interaction of memory Th2 cells and some of the mechanistics behind the importance of the peritoneal cavity (PEC) for early recall responses to intestinal nematodes. We could show that in mice, memory Th2 cells with distinct transcriptional profiles persist systemically in both lymphoid and non-lymphoid tissues up to 3 months post-cure of infection with the small intestinal nematode H. polygyrus. Furthermore, cured mice harboured PEC-resident memory Th2 cells with stronger cytokine production and elevated expression of the costimulatory marker Ox40 as early as 3 days post-challenge infection, compared with small intestinal lamina propria (siLP), mesenteric lymph nodes (mLN) or the lung. Moreover, PEC-resident Ox40+ memory Th2 cells display elevated expression of the activation marker CD69 and IL-5, and upregulate Ox40 expression and IL-5 production in a parasite-specific manner – a response restricted to the PEC compartment. An influx of Ox40 ligand (Ox40L)-expressing dendritic cells (DC) and eosinophils were also observed in the peritoneum of cured mice 3 days post-secondary H. polygyrus infection. In summary, our current work shows that the murine peritoneal cavity harbours early Th2 recall responses to a challenge nematode infection, marked by infiltration of Ox40+ memory Th2 cells, Ox40L+ dendritic cells and eosinophils, highlighting the importance of the PEC for immunological memory to nematodes.