Mycobacterium tuberculosis infection modulates adipose tissue biology

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dc.citation.issue10
dc.citation.volume13
dc.contributor.authorBeigier-Bompadre, Macarena
dc.contributor.authorMontagna, Georgina N. [UNIFESP]
dc.contributor.authorKuehl, Anja A.
dc.contributor.authorLozza, Laura
dc.contributor.authorWeiner, January, III
dc.contributor.authorKupz, Andreas
dc.contributor.authorVogelzang, Alexis
dc.contributor.authorMollenkopf, Hans-Joachim
dc.contributor.authorLoewe, Delia
dc.contributor.authorBandermann, Silke
dc.contributor.authorDorhoi, Anca
dc.contributor.authorBrinkmann, Volker
dc.contributor.authorMatuschewski, Kai
dc.contributor.authorKaufmann, Stefan H. E.
dc.coverageSan Francisco
dc.date.accessioned2020-08-04T13:40:07Z
dc.date.available2020-08-04T13:40:07Z
dc.date.issued2017
dc.description.abstractMycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extra-pulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection. Mice infected via aerosol showed infiltration of inducible nitric oxide synthase (iNOS) or arginase 1 (Arg1)-negative F4/80(+) cells, despite recruitment of CD3(+), CD4(+) and CD8(+) T cells. Gene expression analysis of adipose tissue of aerosol Mtb-infected mice provided evidence for upregulated expression of genes associated with T cells and NK cells at 28 days post-infection. Strikingly, IFN-gamma-producing NK cells and Mtb-specific CD8(+) T cells were identified in perigonadal fat, specifically CD8(+) CD44(-) CD69(+) and CD8(+) CD44(-) CD103(+) subpopulations. Gene expression analysis of these cells revealed that they expressed IFN-gamma and the lectin-like receptor Klrg1 and downregulated CD27 and CD62L, consistent with an effector phenotype of Mtb-specific CD8(+) T cells. Sorted NK cells expressed higher abundance of Klrg1 upon infection, as well. Our results reveal the ability of Mtb to persist in adipose tissue in a stressed state, and that NK cells and Mtb-specific CD8(+) T cells infiltrate infected adipose tissue where they produce IFN-gamma and assume an effector phenotype. We conclude that adipose tissue is a potential niche for Mtb and that due to infection CD8(+) T cells and NK cells are attracted to this tissue.en
dc.description.affiliationMax Planck Inst Infect Biol, Dept Immunol, Berlin, Germany
dc.description.affiliationMax Planck Inst Infect Biol, Parasitol Unit, Berlin, Germany
dc.description.affiliationCharite, Div Gastroenterol Infectiol & Rheumatol, Med Dept, Berlin, Germany
dc.description.affiliationMax Planck Inst Infect Biol, Core Facil, Berlin, Germany
dc.description.affiliationUniv Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationJames Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biosecur & Trop Infect Dis, Cairns, Qld, Australia
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipEuropean Unions Seventh Framework Programme for Research, Technological Development and Demonstration [305279 TANDEM]
dc.description.sponsorshipADITEC [HEALTH-F4-2011-280873]
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1371/journal.ppat.1006676
dc.identifier.citationPlos Pathogens. San Francisco, v. 13, n. 10, p. -, 2017.
dc.identifier.doi10.1371/journal.ppat.1006676
dc.identifier.fileWOS000414163300028.pdf
dc.identifier.issn1553-7366
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57299
dc.identifier.wosWOS:000414163300028
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos Pathogens
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleMycobacterium tuberculosis infection modulates adipose tissue biologyen
dc.typeinfo:eu-repo/semantics/article
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