Publikationsdatenbank

The Th2 effector response to tissue migrating Ascaris suum infection is locally restricted, transient, and antigen-specific (2022)

Art

Vortrag

Autoren

Oser, L. (WE 6)

Hartmann, S. (WE 6)

Ebner, F. (WE 6)

Kongress

Research Training Group 2046: retreat 27. + 28.10.2022

Berlin, 27. – 28.10.2022

Quelle

Sprache

Englisch

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

Ascaris suum, similar to its human counterpart A. lumbricoides, is one of the most relevant and prevalent soil-transmitted helminths detected in swine. In both pigs and humans, protective immunity against recurrent infection develops slowly. Moreover, the distribution pattern of Ascarids, as many other nematodes, is typically heterogenic and overdispersed. While A. suum infections in pigs represent a highly relevant model for human Ascariasis, the development and characterization of type 2 immunity in Ascaris-infected swine is insufficiently described. Therefore, this PhD project aims to investigate the various aspects of protective (Th2) and nonprotective (Th1) responses against A. suum in swine, focusing on: i) the local and systemic adaptive immune responses to the initial tissue migration and worm maturation, ii) how frequency/functional properties of parasite-specific T cells are associated with parasite overdispersion, and iii) the role of T cell phenotypes in reinfection.
Therefore, we analyzed systemic and local immune responses in migration-associated organs and their draining lymph nodes at distinct time points following infection. Our current findings indicate that during primary, subclinical A. suum infection larval migration triggers a localized and transient Th2 response in the lungs but not the liver. When larvae return to the small intestine, gut restricted Th2 responses are similarly detected and increase while Ascaris worms mature and develop into adults. However, we did not detect signs for a systemic Th2 response in spleen or blood of infected pigs. In parallel, we observed the development of Th1-biased responses both systemically and at multiple local sites. Thus, we investigated whether Ascaris suum directly elicits Th1-biased responses by antigen-specific T cell enrichment. Data suggests that the majority of Ascaris-specific CD4+ T cells throughout the infection process produce predominantly IL-4 and to a much lesser extent IFNg. A follow up experiment revealed that infecting pigs with high doses of A. suum eggs succeeds in inducing systemic Th2 immunity, but only during acute, and not chronic infection.
Based on our findings, we propose that the concurrent increase in type 1 immunity observed in developing pigs potentially counteracts efficient and systemic Th2 responses and might contribute to chronicity and constant reinfection. Further investigation is afoot to study the consequences on heterogeneity and predisposition to Ascaris suum in swine.