Mycobacterium tuberculosis Infection Modulates Adipose Tissue Biology

ABSTRACT: Mycobacterium tuberculosis (Mtb) primarily resides in the lung but it can also persist in extrapulmonary 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. In addition, Mtb infection induces changes in adipose tissue biology depending on the route of administration and stage of infection. At day 14 post-systemic Mtb infection, F4/80+ (inducible nitric oxide synthase-positive) iNOS+ cells (M1 macrophages) as well as CD3, CD4 and CD8 T cells were present, and by day 28, B220+ cells had arrived in adipose tissue. In contrast, mice infected via aerosol only showed infiltration of F4/80+ cells that do not express iNOS or arginase 1 (Arg1) and 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. Moreover, IFN-gamma-producing NK cells and Mtb-specific CD8 T cells were found in perigonadal fat, specifically CD8+CD44-CD69+ and CD8+CD44-CD103+ subpopulations. Gene expression analysis of selected NK cells and Mtb-specific CD8 T cells in perigonadal fat of infected mice revealed that they produced IFN-gamma and transcribed the lectin-like receptor Klrg1 whereas CD27 and CD62L transcript levels were downregulated consistent with an effector phenotype. Sorted NK cells expressed higher levels 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- and assume an effector phenotype. We conclude that Mtb exploits adipose tissue as niche, to which CD8 T cells and NK cells are attracted.

ORGANISM(S): Mus musculus

PROVIDER: GSE83554 | GEO | 2017/10/12

SECONDARY ACCESSION(S): PRJNA326334

REPOSITORIES: GEO