Publication Database

Repeated low-dose infection with Ascaris suum induces immunological long-term memory with a rapid protective effector response in the liver (2021)

Art

Vortrag

Autoren

Schlosser-Brandenburg, Josephine (WE 6)

Ebner, Friederike (WE 6)

Kühl, Anja A.

Rausch, Sebastian (WE 6)

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=117&tx_coprogramm_programm%5Bsession%5D=20&tx_coprogramm_programm%5BcurrentPage%5D=&tx_coprogramm_programm%5Baction%5D=programm&tx_coprogramm_programm%5Bcontroller%5D=Source&cHash=c0bafe6210dd185f7dabcabf82d751e8

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

The roundworm Ascaris is one of the most widespread parasites worldwide, infecting humans and livestock alike. Via the intestinal epithelial barrier, infective larvae enter the portal bloodstream of the host and begin extensive tissue migration through the liver, followed by the lungs. An effective vaccine is urgently needed to complement anthelmintic deworming strategies and enable a more sustainable approach toward infection control. Ideally, immunization should result in immobilization/killing of the migrating larvae already during the initial phase of migration through the liver, thus minimizing tissue pathology. However, protective mechanisms during tissue migration leading to larval arrest are still speculative.

Thus, we aimed to investigate whether long-lasting protection can be achieved by repeated low-dose infection and addressed the cellular signatures involved in protective immunity in the liver. Mice were repeatedly inoculated with embryonated Ascaris suum eggs and challenged 10 weeks after the last administration. Protective immune responses were compared in two different mouse strains to investigate whether intrinsic differences in susceptibility to primary Ascaris infection do influence memory formation and liver pathology.

A Th2 central/effector memory pool was established in blood following low-dose infections. 10 weeks after the treatments, both reinfected strains were almost completely protected from tissue migration towards the lungs, as only very few larvae were detected in lung tissue and bronchioalveolar lavage fluid. In the liver of the protected animals a high number of IL-5 and IL-6 producing ILC2 and a significant proportion of IL-13 producing A. suum antigen-specific Th2 cells were detected, with eosinophils recruited into the tissue rapidly after challenge. Serum alanine aminotransferase activity was reduced compared to naïve controls, indicating reduced liver damage. A. suum-specific IgG1 and IgE were detected in the serum of both strains, while A. suum-specific IgA was detected only in bile of the intrinsically more susceptible strain.

In conclusion, our results suggest that the liver plays a crucial role in the formation of protective memory immune responses to A. suum infection, resulting in larval arrest. Protection against infection correlates with strong type 2 immune responses in the liver, while intrinsic differences in hepatic immunity may contribute to differences in host susceptibility during larval migration.