Mycobacterium tuberculosis can gain access to adipose depots of mice infected via the intra-nasal route and to lungs of mice with an infected subcutaneous fat implant

• In intra-nasally infected mice, Mycobacterium tuberculosis disseminates from lungs to distant adipose depots.
• Dissemination takes place even with an infection dose as low as 102 bacilli.
• The bacilli disseminates to visceral, subcutaneous and perirenal adipose depots.
• Bacterial load in adipose depots are higher in the chronic infection phase.
• M. tuberculosis can disseminate to the lungs from a subcutaneous adipocyte implant.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis has the remarkable ability to persist as non-replicating forms in the host. These persisters are tolerant to drugs targeting actively replicating bacilli and hence are responsible for the need of an extended duration of anti-tubercular therapy. The anatomical locations and cell types housing Mtb persisters are being investigated in the recent times. Adipose tissue and the adipocytes are proposed niches of Mtb persisters. In the present study, we carried out experiments in the immunocompetent Swiss mice to see the dissemination of Mtb from lungs to adipose tissue and vice versa. Mice infected intra-nasally with ∼106, 104 or 102 bacilli harboured Mtb in various adipose depots distal to the lungs such as the visceral, subcutaneous and peri-renal depots. The dissemination was minimal at two weeks post-infection, as evident from culture negative adipose tissue samples. But at seven weeks post-infection, viable Mtb could be detected in 78%, 66% and 66% of the samples from high, moderate and low dose-infection groups respectively. In a separate experiment, Mtb-infected pre-adipocytes were implanted subcutaneously to un-infected mice. At five weeks post-implantation, the intact implants had a mean 7 ± 0.53 log10 CFUs/100 mg tissue, while the lungs had a mean 3.25 ± 0.32 log10 CFUs/100 mg tissue. In conclusion, the study shows that Mtb can disseminate from lungs to distant adipose depots and vice versa.