Th2 memory responses to an intestinal helminth infection

• Applicant: Professorin Dr. Susanne Hartmann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 396638922

The current funding period revealed three main aspects of Th2 memory against intestinal nematodes: (i) the peritoneum plays a key role in the maintenance of memory Th2 cells after abrogation of primary infection; (ii) immunization with helminth excretory/secretory (E/S) products induces a level of protection similar to that of natural infection against reinfection, which specifically depends on long-lived functional memory T cells; (iii) Th2 memory cell formation, tissue distribution, and recall response are independent of host microbiota. Based on these findings, we aim to expand the knowledge of the mechanisms of Th2 memory cell recruitment and reactivation against intestinal helminths in the prolongation phase. The following hypotheses will be investigated: A) The peritoneum is essential for the recirculation of effector and memory Th2 cells for a protective immune response against intestinal nematodes. This will be investigated by a) adoptive transfers to determine whether peritoneal memory Th2 cells migrate to the small intestine upon re-infection with nematodes and b) blocking cellular adhesion markers to decipher whether their interaction is essential for recruitment, retention and relocalization of peritoneal Th2 cells. B) Cytokine environment and local antigen presentation in the peritoneal cavity are essential for Th2 memory cell reactivation. Here, we plan to focus on the role of IL-27 as a regulator of Th2 memory cell formation and reactivation in the peritoneum and to investigate whether the reactivation of Th2 memory cells in the peritoneum after infection is an antigen-dependent process. C) Mesenteric fat is an important reservoir of Th2 memory cells in intestinal nematode infections and promotes protective immune responses against parasite E/S products. Based on preliminary data showing that mesenteric fat contains Th2 memory cells more than a year after primary nematode infection, we aim to decipher whether Th2 cells interact with adipocytes during primary infection, memory stage, and reinfection with gastrointestinal nematodes and after immunization with E/S products of intestinal nematodes.

• DFG Programme: Research Grants