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Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice
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 p...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368192/ https://www.ncbi.nlm.nih.gov/pubmed/35967418 http://dx.doi.org/10.3389/fimmu.2022.923754 |
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author | 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. |
author_facet | 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. |
author_sort | Cabana-Puig, Xavier |
collection | PubMed |
description | 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 CX(3)CR1-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. |
format | Online Article Text |
id | pubmed-9368192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93681922022-08-12 Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice 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. Front Immunol Immunology 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 CX(3)CR1-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. Frontiers Media S.A. 2022-07-28 /pmc/articles/PMC9368192/ /pubmed/35967418 http://dx.doi.org/10.3389/fimmu.2022.923754 Text en Copyright © 2022 Cabana-Puig, Mu, Lu, Swartwout, Abdelhamid, Zhu, Prakash, Cecere, Wang, Callaway, Sun, Reilly, Ahmed and Luo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology 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. Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice |
title |
Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice |
title_full |
Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice |
title_fullStr |
Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice |
title_full_unstemmed |
Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice |
title_short |
Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice |
title_sort | lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone mrl/lpr mice |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368192/ https://www.ncbi.nlm.nih.gov/pubmed/35967418 http://dx.doi.org/10.3389/fimmu.2022.923754 |
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