Dietary antigen acquisition by lamina propria (LP) dendritic cells (DCs) is crucial to induce oral tolerance and maintain homeostasis. However, encountering innocuous antigens during infection can lead to inflammatory responses, suggesting processes may limit steady-state luminal antigen capture during infection. We observed that goblet cell (GC) associated antigen passages (GAPs), a steady-state pathway delivering luminal antigens to LP-DCs, are inhibited during Salmonella infection. GAP inhibition was mediated by IL-1β. Infection abrogated luminal antigen delivery and antigen-specific T cell proliferation in the mesenteric lymph node (MLN). Antigen-specific T cell proliferation to dietary antigen was restored by overriding GAP suppression; however, this did not restore regulatory T cell induction, but induced inflammatory T cell responses. Salmonella translocation to the MLN required GCs and correlated with GAPs. Genetic manipulations overriding GAP suppression, or antibiotics inducing colonic GAPs, but not antibiotics that do not, increased dissemination and worsened outcomes independent of luminal pathogen burden. Thus, steady-state sampling pathways are suppressed during infection to prevent responses to dietary antigens, limit pathogen entry, and lessen the disease. Moreover, antibiotics may worsen Salmonella infection by means beyond blunting gut microbiota colonization resistance, providing new insight into how precedent antibiotic use aggravates enteric infection.

中文翻译：

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鼠伤寒沙门氏菌感染期间，杯状细胞相关抗原通道受到抑制，以防止病原体传播并限制对饮食抗原的反应。

固有层 (LP) 树突状细胞 (DC) 获取饮食抗原对于诱导口服耐受和维持体内平衡至关重要。然而，在感染过程中遇到无害抗原可能会导致炎症反应，这表明该过程可能会限制感染过程中稳态管腔抗原的捕获。我们观察到，杯状细胞 (GC) 相关抗原通道 (GAP)（一种将管腔抗原递送至 LP-DC 的稳态途径）在沙门氏菌感染期间受到抑制。GAP 抑制由 IL-1β 介导。感染消除了肠系膜淋巴结 (MLN) 中的管腔抗原递送和抗原特异性 T 细胞增殖。通过克服 GAP 抑制，恢复了针对饮食抗原的抗原特异性 T 细胞增殖；然而，这并没有恢复调节性 T 细胞的诱导，而是诱导了炎症 T 细胞反应。沙门氏菌易位至 MLN 需要 GC，并与 GAP 相关。超越 GAP 抑制的基因操作，或诱导结肠 GAP 的抗生素（但不诱导结肠 GAP 的抗生素则不然），会增加传播并使结果恶化，而与肠腔病原体负荷无关。因此，在感染过程中稳态采样途径受到抑制，以防止对饮食抗原的反应，限制病原体进入并减轻疾病。此外，抗生素可能会通过削弱肠道微生物群定植抵抗力之外的方式恶化沙门氏菌感染，这为了解先前抗生素的使用如何加剧肠道感染提供了新的见解。