Publikationsdatenbank

Liver-draining portal lymph node responds to enteric nematode infection by generating highly parasite-specific follicular T helper and B cell responses (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Adjah, Joshua (WE 6)

D. Musimbi, Zaneta (WE 6)

Mugo, Robert M. (WE 6)

Midha, Ankur (WE 6)

Hartmann, Susanne (WE 6)

Rausch, Sebastian (WE 6)

Quelle

Frontiers in immunology

Bandzählung: 16

Seiten: 1483274

ISSN: 1664-3224

Sprache

Englisch

Verweise

URL (Volltext): https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1483274/full

DOI: 10.3389/fimmu.2025.1483274

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

Introduction
While research on the gut-liver axis in non-communicable liver diseases has expanded exponentially, few studies have investigated the liver-gut relationship in the context of gastrointestinal nematode infections. This study aimed to determine whether liver-draining lymph nodes (LLNs) contribute to the immune response against a strictly enteric nematode infection.

Methods
We analyzed the cellular and functional immune responses in the portal (PLN) and celiac (CLN) liver-draining lymph nodes following infection with the small intestinal nematode Heligmosomoides (polygyrus) bakeri (H. bakeri). The composition of dendritic cells and CD4+ T cell subsets in LLNs was compared to the mesenteric lymph nodes (MLN), the primary draining site of gut infections. Additionally, we examined Th2 effector cell expansion, plasmablast generation, and B cell activation across these lymphoid sites.

Results
Both PLN and CLN exhibited increased cellularity at d14 post-infection. The immune profile in CLN closely resembled that of MLN, characterized by a robust expansion of GATA-3+ Th2 effector cells at days 6 and 14 post-infection. This was accompanied by an early plasmablast response, producing low-affinity IgG1 antibodies targeting immune-dominant excretory-secretory (ES) products. In contrast, PLN showed weaker Th2 responses and lower early plasma cell responses compared to MLN and CLN. However, PLN displayed strong follicular T helper (TFH) activity, with a B cell profile biased toward germinal center reactions. This led to high-affinity IgG1 antibodies specifically binding VAL-1 and ACE-1.

Discussion
These findings demonstrate, for the first time, that liver-draining lymph nodes actively participate in the adaptive immune response to enteric nematode infections. While MLN and CLN function synergistically in generating early Th2 effector cells and rapid extrafollicular IgG1+ plasma cell responses, PLN specializes in TFH-driven germinal center reactions and affinity maturation.