Adjah Joshua, D Musimbi Zaneta, Mugo Robert M, Midha Ankur, Hartmann Susanne, Rausch Sebastian
Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany.
Front Immunol. 2025 Feb 28;16:1483274. doi: 10.3389/fimmu.2025.1483274. eCollection 2025.
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.
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 . 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.
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.
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.
虽然关于非传染性肝病中肠-肝轴的研究呈指数级增长，但很少有研究在胃肠道线虫感染的背景下探讨肝-肠关系。本研究旨在确定引流肝脏的淋巴结（LLN）是否有助于针对严格肠道线虫感染的免疫反应。
我们分析了小肠线虫感染后门静脉（PLN）和腹腔（CLN）引流肝脏的淋巴结中的细胞和功能性免疫反应。将LLN中树突状细胞和CD4+ T细胞亚群的组成与肠道感染的主要引流部位肠系膜淋巴结（MLN）进行了比较。此外，我们检查了这些淋巴部位的Th2效应细胞扩增、浆母细胞生成和B细胞活化情况。
感染后第14天，PLN和CLN的细胞数量均增加。CLN中的免疫谱与MLN非常相似，其特征是感染后第6天和第14天GATA-3+ Th2效应细胞大量扩增。这伴随着早期浆母细胞反应，产生针对免疫显性排泄-分泌（ES）产物的低亲和力IgG1抗体。相比之下，与MLN和CLN相比，PLN的Th2反应较弱，早期浆细胞反应较低。然而，PLN表现出强烈的滤泡辅助性T细胞（TFH）活性，其B细胞谱偏向生发中心反应。这导致高亲和力IgG1抗体特异性结合VAL-1和ACE-1。
这些发现首次证明，引流肝脏的淋巴结积极参与对肠道线虫感染的适应性免疫反应。虽然MLN和CLN在产生早期Th2效应细胞和快速滤泡外IgG1+浆细胞反应方面协同发挥作用，但PLN专门负责TFH驱动的生发中心反应和亲和力成熟。
