ABSTRACT
The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
WHZ and YX, resources; HBS, SFW, LLL, QS and YX, data curation; SFW, LLL, WJ and YX, software; HBS, LLL, WJ and YX, formal analysis; HBS, SFW, LLL, YTL, HXM and YMH, validation; SFW, LLL, YTL, HXM, WJ and YMH, investigation; HBS, WHZ, QS and YX, visualization; HBS, WJ, SFW, LLL, HHW and YX, methodology; HBS and YX, writing of the original draft; HBS, WHZ and YX, writing the review and editing; HBS, HHW, WHZ and YX, funding acquisition; HHW, WHZ and YX, project administration; HBS and YX, conceptualization; HBS, HHW, WHZ and YX, supervision. The order among co-first authors is determined by their contribution to performing experiments and writing the manuscript.
Data availability statement
All data generated or analyzed during this study are included in this article and its supplementary information files. Further inquiries can be directed to the corresponding author.
Materials availability
This study did not generate new unique reagents.