Publikationsdatenbank

High resistance to intestinal nematode infection is associated with a strong bias for follicular T helper cell responses, rapid IgG1 class switch and limited Th2 effector cell expansion (2021)

Art

Vortrag

Autoren

Hongwei, Zhang (WE 6)

Hartmann, Susanne (WE 6)

Rausch, Sebastian (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=244&tx_coprogramm_programm%5Bday%5D=&tx_coprogramm_programm%5Baction%5D=programm&tx_coprogramm_programm%5Bcontroller%5D=Source&cHash=196bea0ba352f35ce41fced3f97c9fd7

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

Gastrointestinal nematode infections are highly prevalent in nature, lead to considerable morbidity in infected humans and cause high economical loss in animal husbandry. While it is clear that type 2 responses orchestrated by CD4+GATA-3+ Th2 cells are pivotal for the control of GI nematodes, the basis for differential susceptibility of distinct host genetic backgrounds is less well understood.

The high resistance of "rapid responder" SJL mice to infections with the small intestinal nematode H. polygyrus is evident in low parasite egg production and the termination of infection within a few weeks. Comparing the SJL line to slow responder C57BL/6 mice, we found that SJL mice generated relatively few, but mostly parasite-specific Th2 effector cells in gut draining lymph nodes, which seemed sufficient for rapid M2 polarization and the formation of type 2 granuloma around tissue-dwelling nematode larvae. By contrast, susceptible C57BL/6 mice displayed extensive expansion of poorly parasite-specific Th2 cells in both mLN and spleen. These expressed low levels of the gut/mucosal homing markers CCR9/a4b7, resulting in the delayed accumulation of Th2 cells in the infected small intestine. Surprisingly, resistance was further associated with exceptionally high proportions of Treg in the spleen of SJL mice at steady state and the vigorous expansion of Treg in mLN after infection. This coincided with a bias for follicular T helper cells expansion in both mLN and spleen and, consequently, more extensive IgG1 class switching by GL7+ germinal center B cells in both organs.

In conclusion, resistance versus susceptibility to primary H. polygyrus infection appears to be less dependent on the overall magnitude of Th2 responses, but rather seems to depend on follicular T helper cells and the rapid instruction of antibody responses. In order to prove this, we currently evaluate protective immunity transferred by infection-derived B cells and the role of Treg in the balance of Th2 effector vs. TFH differentiation.