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

Joshua Adjah ^* Zaneta D. Musimbi Robert Mugendi Mugo Ankur Midha Susanne Hartmann Sebastian Rausch ^*

• Institute of Immunology, Department of Veterinary Medicine, Free University of Berlin, Berlin, Germany

Contrasting an exponential rise of studies addressing the gut/liver axis in non-communicable liver disease, few studies have explored the intricate relationship between the liver and the gut in the context of gastrointestinal nematode infections. Here, we asked whether the liverdraining LNs participate in the immune response to a strictly enteric nematode infection. The cellularity of both the portal and celiac liver lymph nodes (PLN and CLN) increased in infections with the small intestinal nematode Heligmosmoides (polygyrus) bakeri (H. bakeri), whereby the phenotypical composition of dendritic cells and CD4+ T cell populations determined in CLN roughly reflected the response seen in mesenteric lymph nodes (MLN). The response in both CLN and MLN was marked by the strong expansion of GATA-3+ Th2 effector cells at day 6 and 14 post-infection, coinciding with similar early plasmablasts response serving as early sources of low-affinity IgG1 antibodies, which primarily recognized immune-dominant ES products. In contrast, the PLN harbored less extensive Th2 responses and lower early plasma cell responses compared to MLN and CLN. However, robust follicular T helper cell activity and a B cell profile biased for germinal center reactions corroborated with superior B cell functional capacity evident in high-affinity IgG1 antibodies, binding both VAL-1 and ACE-1. Hence, this study shows for the first time that the liver-draining LNs take part in the adaptive immune response to enteric nematode infections. MLN and CLN synergize functionally in the early output of Th2 effector cells and in rapid extrafollicular IgG1+ plasma cell generation. In contrast, the response in PLN is biased for TFH responses and thereby provides an environment highly suited for germinal center reactions and affinity maturation.