Publikationsdatenbank

Genotype- and age-dependent intestinal T cell homing, and liver-associated immune responses in enteric nematode infection (2025)

Art

Hochschulschrift

Autor

Adjah, Joshua (WE 6)

Quelle

Berlin: Mensch und Buch Verlag, 2025 — X, 130 Seiten

ISBN: 978-3-96729-293-0

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/48647

Kontakt

Institut für Immunologie

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

Abstract / Zusammenfassung

Background: Studies in mice infected with gastrointestinal (GI) nematodes, particularly Heligmosomoides polygyrus bakeri (H. bakeri), provide critical insights into the immune factors that govern resistance to infection. Resistance to H. bakeri is primarily mediated by high levels of GATA-3+ CD4+ Th2 cells in mesenteric lymph nodes (MLN). Two mouse strains are commonly studied: BALB/c mice, which efficiently clear the infection within weeks, and C57BL/6 mice, which are more susceptible, often carrying the infection for months, making them a useful model for chronic infection research. Age impacts resistance in BALB/c mice, with older mice showing reduced immunity due to slower effector cell migration to the infection site. This study explores whether resistance to H. bakeri infection is influenced by both genetic and age-related factors affecting effector cell recruitment to the infected gut. Additionally, the research examines the role of liver-draining lymph nodes (celiac lymph node; CLN, portal lymph node, PLN) in immune response modulation and the interplay between the liver and gut during infection, analyzing how these affect the liver metabolic microenvironment and shape immune response and infection outcome. Aims: 1. To determine whether genotype and age influence resistance to H. bakeri infection 2. To investigate how these factors modulate the speed and efficiency of effector cell recruitment 3. To elucidate the role of liver-draining lymph nodes (LLNs) in the differentiation of classical Th2 and Th2/1 hybrid cells 4. To explore the potential impact of co-drainage between the MLN and LLNs on immune responses 5. To explore the interaction between liver and T cells during H. bakeri infection Results: We show that in resistant BALB/c mice, rapid Th2 cell recruitment to the gut, driven by CCR9 expression and specific dendritic cells, effectively limits early H. bakeri larval development. In contrast, delayed Th2 responses in susceptible C57BL/6 mice allow larvae to mature into adult worms, while aging BALB/c mice also experience reduced Th2 homing, diminishing their resistance. Additionally, liver-draining lymph nodes contribute to immunity byexpanding Th2 cells (CLN) and supporting high-affinity IgG1 antibody production (PLN). Liver-resident T cells produce high levels of IL-5, IL-4, and IL-13 in a glucose-rich environment, which enhances their immune functionality. Conclusion: This study demonstrates that BALB/c mice resist H. bakeri infection more effectively than C57BL/6 mice due to enhanced CCR9 expression and swift Th2 cell recruitment to the gut. In older BALB/c mice, reduced ALDH activity and delayed Th2 recruitment weaken resistance. Furthermore, despite limited Th2 activity, PLN compensates with strong TFH bias, forming more GCs that produce high-affinity antibodies. The liver also plays a key immune role by sustaining Th2/1 responses through IFN-γ, CXCR3, and metabolic adaptations. This highlights the liver’s potential as a target for optimizing immune response modulation in intestinal helminth infections.