Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice

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dc.contributor.authorCabana-Puig, Xavieren
dc.contributor.authorMu, Qinghuien
dc.contributor.authorLu, Ranen
dc.contributor.authorSwartwout, Briannaen
dc.contributor.authorAbdelhamid, Leilaen
dc.contributor.authorZhu, Jingen
dc.contributor.authorPrakash, Meetaen
dc.contributor.authorCecere, Thomas E.en
dc.contributor.authorWang, Zhuangen
dc.contributor.authorCallaway, Sabrinaen
dc.contributor.authorSun, Shaen
dc.contributor.authorReilly, Christopher M.en
dc.contributor.authorAhmed, S. Ansaren
dc.contributor.authorLuo, Xin M.en
dc.date.accessioned2023-02-01T13:22:52Zen
dc.date.available2023-02-01T13:22:52Zen
dc.date.issued2022-07-28en
dc.date.updated2023-01-31T20:47:49Zen
dc.description.abstractCommensal 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fimmu.2022.923754en
dc.identifier.eissn1664-3224en
dc.identifier.issn1664-3224en
dc.identifier.orcidCecere, Thomas [0000-0001-9558-0615]en
dc.identifier.pmid35967418en
dc.identifier.urihttp://hdl.handle.net/10919/113607en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35967418en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectLactobacillusen
dc.subjectdouble-negative T cellsen
dc.subjectgut microbiotaen
dc.subjectlupusen
dc.subjectmemory T cellsen
dc.subjecttype 1 regulatory T cellsen
dc.subjectAutoimmune Diseaseen
dc.subjectInflammatory and immune systemen
dc.subject.meshAnimalsen
dc.subject.meshMice, Inbred MRL lpren
dc.subject.meshMiceen
dc.subject.meshLactobacillusen
dc.subject.meshSplenomegalyen
dc.subject.meshDysbiosisen
dc.subject.meshLymphadenopathyen
dc.titleLactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr miceen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-07-06en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen

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