Publikationsdatenbank

Liver macrophage polarization is associated with resistance and susceptibility to Ascaris infection (2022)

Art

Vortrag

Autoren

Elizalde‐Velázquez, Luis E. (WE 6)

Schlosser-Brandenburg, J. (WE 6)

Kühl, A.A.

Hartmann, S. (WE 6)

Kongress

VIA Meeting 2022

Hannover, 06. – 07.09.2022

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

Ascariasis, one of the most prevalently neglected tropical diseases in the world affecting humans and pigs alike, shows an overdispersion in infected hosts. Reasons for this marked variability in worm burden are still unknown. We hypothesize intrinsic genetic differences in immune cell composition and macrophage phenotypes account for the overdispersion.
We infected two mouse strains mimicking the hepato-tracheal migration of Ascaris suum larvae in its natural hosts but showing contrasting phenotypes to infection. Our data show drastically reduced Ascaris suum larvae in the liver as well as decreased liver pathology in the resistant mice (CBA) at day 4 p.i. indicating the liver as prime organ facilitating resistance against Ascaris hepato-tracheal migration. Interestingly, hepatic resistance against Ascaris larval migration was associated with differences in polarization of liver macrophages. Intrinsically, the frequencies of alternatively activated (M2) macrophages were elevated in the liver of the resistant strain (CBA) in comparison to susceptible mouse strain (C57BL/6). Ascaris infection, at day 4 pi., led to a hepatic downregulation of this intrinsic host protective macrophage response which might be attributed to Ascaris larvae immune modulation. However, the resistant CBA mice showed a significant M2 polarization of macrophages also in the lung as well as systemically depicted in the spleen which led to a potent overall type 2 immune response and protection against infection.
Therefore, resistance against migrating Ascaris larvae is associated with intrinsic liver M2 polarization and an enhanced induction of a systemic M2 polarization.