Mycobacterium canettii Infection of Adipose Tissues

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.

Triacylglycerols: Fuelling the Hibernating Mycobacterium tuberculosis

“…Mtb inside adipocytes also accumulate ILIs (Neyrolles et al, 2006; Agarwal et al, 2014). M. canettii has been shown to replicate and accumulate ILIs inside brown and white preadipocytes (Bouzid et al, 2017). However, a more recent study demonstrated that macrophage lipid body formation during Mtb infection is part of an adaptive immune response activated by IFN-γ (Knight et al, 2018).…”

The response of adipose tissues to <i>Mycoplasma pulmonis</i> and Sendai virus infection in C57BL/6 and DBA/2 mice

“…These cells participate in whole-body immune signaling via secretion of adipokines and cytokines such as adiponectin, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 [ 3 ]. Moreover, white adipose tissue (WAT), brown adipose tissue (BAT), and adipocytes are targets of many pathogens such as Trypanosoma cruzi [ 15 ], Staphylococcus aureus [ 25 ], Mycobacterium canettii [ 6 ], and Mycobacterium tuberculosis [ 3 ], resulting in a change of adipose tissue. However, the function of adipose tissue in the progression and pathology of pathogens during infection is remained unclear.…”

Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone

“…The adaptation of M. ulcerans to its new environment was reflected by a larger proportion of bacteria containing ILIs during healing than at the edema stage. The incorporation of host-derived fatty acids into mycobacterial lipid inclusion [ 46–49 ], or directly into mycobacterial membranes [ 50 ] has already been reported. Thus, in times of starvation, M. ulcerans may hydrolyze stored lipids to satisfy its nutrition and energy requirements, as already suggested for M. tuberculosis during latency and reactivation [ 50–53 ].…”