Publication Database

Prominent Th1 and Treg responses in wild mice infected with intestinal nematodes (2021)

Art

Vortrag

Autoren

Zhang, Hongwei (WE 6)

Bednár, Lubomir

Heitlinger, Emanuel

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=223&tx_coprogramm_programm%5Bday%5D=&tx_coprogramm_programm%5Baction%5D=programm&tx_coprogramm_programm%5Bcontroller%5D=Source&cHash=a334c3496d5603c50acbb566b8b94516

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

Laboratory mice have been selected from wild mice and introduced to a controlled environment for nearly 100 years. Considering the consequences of inbreeding, the prevention of contact to the broad spectrum of pathogens faced in nature, and the recent demonstration of distinct gut microbiota profiles of wild and laboratory house mice it is unclear to what extent immunological responses defined in experimental sytems reflect the real situation in nature. In this study, we hence characterized immune parameters of wild house mice (Mus musculus) infected with intestinal nematodes in comparison to worm-free controls.

Of the 95 mice captured around the IZW field station in Niederfinow, 39 were infected with pinworms (mostly Syphacia spp.), 12 harbored whipworms (Trichuris muris) and 3 individuals were co-infected with both. The phenotype of CD4+ T effector cells was determined in spleen and mesenteric lymph nodes (mLN) via flow cytometry based on the expression of transcription factors and cytokines specifying the Th2, Th1 and Th17 lineages, respectively. Contrary to our expectations, nematode infected mice displayed no increase in GATA-3+ Th2 cells, but a highly significant expansion of T-bet+ Th1 cells in both organs, accompanied by significantly elevated frequencies of GATA-3+T-bet+ Th2/1 hybrid cells in the spleen. This mixed response of was confirmed by a highly significant increase in IFN-g production along with a more moderate upregulation of IL-13. In addition, nematode infected mice displayed significantly lower frequencies of RORgt+ Th17 cells, while IL-17A production was barely detectable irrespective of the nematode infection status. Determining the frequencies of Foxp3+ regulatory (Treg) cells in the two wild mouse cohorts we found significantly more Treg in infected mice, which coincided with significantly increased IL-10 expression in infected mice. However, the simultaneous determination of cytokine responses revealed that IFN-g producing Th1 accounted for approximately 50% of the IL-10 production.

In conclusion, elevated Treg responses seen in experimental models of helminth infection are reflected and accompanied by IL-10 producing Th1 cells in wild mice. However, wild mice seem to develop rather modest Th2 responses and display a highly significant increase in Th1 activity, suggesting that the immune strategy of mice responding to nematodes infection in nature differs from the more strongly Th2-biased responses of lab mice.