Mycobacterium tuberculosis (Mtb) primarily resides in the lung but 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. 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-γ-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-γ and the lectin-like receptor Klrg1 and down-regulated 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-γ 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
