Publikationsdatenbank

IL-12 production by porcine myeloid cells following toll-like receptor ligation and Toxoplasma gondii infection (2021)

Art

Poster

Autoren

Hamid, Benjamin (WE 6)

Schlosser-Brandenburg, Josephine (WE 6)

Bechtold, Lalita (WE 6)

Delgadi Betancourt, Estefanía

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=260&tx_coprogramm_programm%5Bsession%5D=44&tx_coprogramm_programm%5BcurrentPage%5D=&tx_coprogramm_programm%5Baction%5D=programm&tx_coprogramm_programm%5Bcontroller%5D=Source&cHash=dded8a205cf482c48f5c4b05903b2efb

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

In mice and humans, infection with Toxoplasma gondii induces a typical Th1 immune response, with monocytes and dendritic cells producing IL-12 shortly after infection. This stimulates natural killer cells and CD8+ T cells to release IFN-γ, and the differentiation of naïve CD4+ T cells into IFN-γ-producing Th1 cells. IFN-γ is the primary driver of resistance to acute T. gondii infection, with this innate response leading to containment of the parasite within tissue cysts in immunocompetent hosts. However, in recent years significant host species-specific differences have been identified. Toll-like receptors 11 and 12 which recognize the soluble T. gondii antigen profilin extracellularly in mice are absent in man, with human myeloid cells requiring phagocytosis of a tachyzoite before responding. The monocyte and dendritic cell subsets which produce IL-12 following recognition are also reversed. The pig is often considered to be an immunologically human-like model, and at first glance it appears this similarity may extend to the response to T. gondii. In pigs, as in humans, postnatal infections usual remain asymptomatic, but congenital toxoplasmosis can cause severe pathology. This contrasts with mice, in which infections can be fatal but fetal infections are rare.

Here we assess the IL-12 responses of porcine peripheral blood monocytes and DC subsets to TLR ligation and T. gondii exposure, both in isolation and in co-culture with lymphocytes. We find that porcine monocytes and cDC do not produce IL-12 following TLR ligation, leaving pDC as the only IL-12-producing myeloid PBMCs in pigs. However, surprisingly, we identify substantial endogenous IL-12 production by porcine CD335+ NK cells following TLR ligation. Interestingly, neither pDC nor NK cells produce IL-12 following exposure to T. gondii tachyzoites. However, IL-18 production by DC was detected following both TLR ligation and live T. gondii tachyzoite exposure, hinting at an alternative mechanism of IFN-γ induction during early T. gondii infection in pigs. Hence, the initial IL-12 response of porcine PBMCs to TLR ligation or T. gondii infection is substantially different than that observed in humans or mice. Porcine CD335+ NK cells serve as important IL-12 producers following TLR ligation, and IL-18 likely plays a prominent role in Th1 induction during early T. gondii infection.