Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice.
Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice.
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DOI：
10.3389/fimmu.2022.923754
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发表时间：
2022
影响因子：
7.3
通讯作者：
Luo, Xin M.
中科院分区：
文献类型：
--
作者：
Cabana-Puig, Xavier;Mu, Qinghui;Lu, Ran;Swartwout, Brianna;Abdelhamid, Leila;Zhu, Jing;Prakash, Meeta;Cecere, Thomas E.;Wang, Zhuang;Callaway, Sabrina;Sun, Sha;Reilly, Christopher M.;Ahmed, S. Ansar;Luo, Xin M.
共生细菌和免疫系统有着密切而牢固的关系，保持平衡以控制炎症。微生物群的改变，称为生态失调，不仅可以在肠粘膜中，而且可以在全身水平上直接与自身抗原反应。我们的实验室先前报道了肠道生态失调，特别是在Lactobacillaceae家族中细菌丰度较低的狼疮易感MRL/lpr小鼠中，这是一种全身性自身免疫模型。用5种不同的乳杆菌属物种（spp.）的混合物恢复微生物群，L. n.罗伊特湖oris，L.约翰逊湖gasseri和L.鼠李糖，减弱狼疮样临床体征，包括脾肿大和淋巴结病。然而，我们对这一机制的理解是有限的。在这项研究中，我们首先研究了单个物种的影响。令人惊讶的是，没有一个物种单独概括了混合的好处。相反，乳杆菌属（Lactobacillus spp.）通过分泌因子和CX 3CR 1依赖性机制协同作用以减轻脾肿大和肾淋巴结病。有趣的是，口服MRS肉汤可能通过增加内源性乳杆菌属的相对丰度而发挥相同的益处。从机制上讲，我们发现在脾和肠系膜淋巴结中给予混合物后，FOXP 3阴性1型调节性T细胞的百分比增加。此外，口服管饲乳杆菌属。降低了中枢记忆T细胞的百分比，同时增加了淋巴器官中效应记忆T细胞的百分比。此外，在含有混合物的脾脏中观察到双阴性T细胞百分比降低。这些结果表明，乳杆菌属。可能作用于T细胞以减轻脾肿大和淋巴结病。总之，这项研究推进了我们对乳酸杆菌如何。减轻MRL/lpr小鼠的狼疮。这些细菌的协同作用表明，多种益生菌的组合可能会抑制系统性自身免疫，使狼疮患者受益。
Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly lower abundance of bacteria in the family Lactobacillaceae, in lupus-prone MRL/lpr mice, a model of systemic autoimmunity. Restoring the microbiota with a mix of 5 different Lactobacillus species (spp.), L. reuteri, L. oris, L. johnsonii, L. gasseri and L. rhamnosus, attenuated lupus-liked clinical signs, including splenomegaly and lymphadenopathy. However, our understanding of the mechanism was limited. In this study, we first investigated the effects of individual species. Surprisingly, none of the species individually recapitulated the benefits of the mix. Instead, Lactobacillus spp. acted synergistically to attenuate splenomegaly and renal lymphadenopathy through secreted factors and a CX3CR1-dependent mechanism. Interestingly, oral administration of MRS broth exerted the same benefits likely through increasing the relative abundance of endogenous Lactobacillus spp. Mechanistically, we found increased percentages of FOXP3-negative type 1 regulatory T cells with administration of the mix in both spleen and mesenteric lymph nodes. In addition, oral gavage of Lactobacillus spp. decreased the percentage of central memory T cells while increasing that of effector memory T cells in the lymphoid organs. Furthermore, a decreased percentage of double negative T cells was observed in the spleen with the mix. These results suggest that Lactobacillus spp. might act on T cells to attenuate splenomegaly and lymphadenopathy. Together, this study advances our understanding of how Lactobacillus spp. attenuate lupus in MRL/lpr mice. The synergistic action of these bacteria suggests that multiple probiotic bacteria in combination may dampen systemic autoimmunity and benefit lupus patients.
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影响因子：
4.6
作者：
López P;de Paz B;Rodríguez-Carrio J;Hevia A;Sánchez B;Margolles A;Suárez A
通讯作者：
Suárez A
DOI：
10.1073/pnas.0503726102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Klebanoff, CA;Gattinoni, L;Restifo, NP
通讯作者：
Restifo, NP
影响因子：
7.3
作者：
Abdelhamid, Leila;Cabana-Puig, Xavier;Luo, Xin M.
通讯作者：
Luo, Xin M.
影响因子：
4.6
作者：
Liao, X.;Ren, J.;Luo, X. M.
通讯作者：
Luo, X. M.
影响因子：
7.5
作者：
Gehad, Ahmed;Teague, Jessica E.;Clark, Rachael A.
通讯作者：
Clark, Rachael A.