CNRS, UMR 7370, LP2M, Faculté de Médecine, University Nice Sophia Antipolis, Nice, France.
University Nice Sophia Antipolis, Nice, France.
Front Immunol. 2019 Apr 2;10:643. doi: 10.3389/fimmu.2019.00643. eCollection 2019.
Intestinal mononuclear phagocytes (MPs) comprise dendritic cells (DCs) and macrophages (Mφs) that play different roles in response to infection. After phagocytosis, DCs expressing CD103 transport from the intestinal tract to the mesenteric lymph nodes (MLN) and induce adaptive immune responses whereas resident Mφs expressing CX3CR1 capture bacteria in the lumen and reside in the (LP) where they induce a local immune response. CX3CR1 Mφs are generated from Ly6C monocytes that enter the colonic mucosa and differentiate locally. We previously demonstrated that the probiotic yeast CNCM I-745 () prevents infection by serovar Typhimurium (ST), decreases ST translocation to the peripheral organs and modifies the pro-and anti-inflammatory cytokine profiles in the gut. In the present study, we investigated the effect of on the migratory CD103 DCs and the resident CX3CR1 Mφs. MPs were isolated from the LP of streptomycin-treated mice infected by ST with or without treatment before or during the infection. In -pretreated mice, we observed a decrease of the CD103 DCs in the LP that was associated with the drop of ST recovery from MLN. Interestingly, induced an infiltration of LP by classical Ly6C monocytes, and modified the monocyte-Mφ maturation process in ST-infected mice. Our results showed that treatment induced the expansion of Ly6C monocytes in the blood as well as in the bone marrow (BM) of mice, thus contributing to the Mφ replenishment in LP from blood monocytes. experiments conducted on BM cells confirmed that induced the expansion of CX3CR1 Mφs and concomitantly ST phagocytosis. Altogether, these data demonstrate that CNCM I-745 modulates the innate immune response. Although here, we cannot explicitly delineate direct effects on ST from innate immunity, -amplified innate immunity correlated with partial protection from ST infection. This study shows that can induce the expansion of classical monocytes that are precursors of resident Mφs in the LP.
肠道单核吞噬细胞 (MPs) 包括树突状细胞 (DCs) 和巨噬细胞 (Mφs)，它们在应对感染时发挥不同的作用。吞噬后，表达 CD103 的 DC 将抗原从肠道运送到肠系膜淋巴结 (MLN)，并诱导适应性免疫反应，而表达 CX3CR1 的驻留 Mφ 在腔中捕获细菌，并驻留在固有层 (LP) 中，诱导局部免疫反应。CX3CR1 Mφ 由进入结肠黏膜并在局部分化的 Ly6C 单核细胞产生。我们之前的研究表明，益生菌酵母 CNCM I-745 () 可预防 血清型鼠伤寒沙门氏菌 (ST) 的感染，减少 ST 向周围器官的转移，并改变肠道中的促炎和抗炎细胞因子谱。在本研究中，我们研究了对迁移性 CD103 DC 和驻留性 CX3CR1 Mφ 的影响。用链霉素处理感染 ST 的小鼠的 LP 中分离 MPs，在感染前后用或不用 进行预处理。在预先用处理的小鼠中，我们观察到 LP 中的 CD103 DC 减少，这与从 MLN 中恢复的 ST 减少有关。有趣的是，诱导经典 Ly6C 单核细胞浸润 LP，并改变 ST 感染小鼠中单核细胞-Mφ 的成熟过程。我们的结果表明，处理诱导了小鼠血液和骨髓 (BM) 中 Ly6C 单核细胞的扩增，从而有助于从血液单核细胞中补充 LP 中的 Mφ。BM 细胞的实验证实，诱导了 CX3CR1 Mφ 的扩增，并同时吞噬 ST。总之，这些数据表明 CNCM I-745 调节先天免疫反应。尽管在这里，我们不能明确地将其与 ST 感染的先天免疫反应区分开来，但增强的先天免疫反应与 ST 感染的部分保护相关。这项研究表明， 可以诱导经典单核细胞的扩增，而经典单核细胞是 LP 中驻留 Mφ 的前体。
