Abstract

Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii, a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18–22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii (p = 0.02) and M. tuberculosis (p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis (p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii, it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.

Highlights

  • In mammals, brown adipose tissue (BAT) and white adipose tissue (WAT) are mainly composed of mature adipocytes, pre-adipocytes and immune cells (Ouchi et al, 2011)

  • Pre-adipocytes purified from murine inguinal WAT and interscapular BAT were ex vivo inoculated with M. canettii or M. tuberculosis for 4 h p.i

  • While negative control cells remained free of detectable mycobacteria, microscopic observations clearly showed intracellular M. canettii and M. tuberculosis in white and brown pre-adipocytes (Figure 1)

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Summary

Introduction

Brown adipose tissue (BAT) and white adipose tissue (WAT) are mainly composed of mature adipocytes, pre-adipocytes and immune cells (Ouchi et al, 2011). In immune-competent mice, intravenously and intra-nasally inoculated M. tuberculosis disseminates in WAT of visceral, subcutaneous, peri-renal and mesenteric adipose depots (Agarwal et al, 2014, 2016). In these models, the burden of M. tuberculosis in WAT depots stagnated or decreased with time (Agarwal et al, 2014). The infection of mature adipocytes was proposed as a suitable model to study the accumulation of neutral lipids into ILIs within mycobacteria (Santucci et al, 2016)

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