Trained immunity contributes to the prevention ofMycobacterium tuberculosisinfection, a novel role of autophagy

Abstract

Mycobacterium tuberculosis (M. tuberculosis) is the pathogen which causes tuberculosis (TB), a significant human public health threat. Co-infection of M. tuberculosis and the human immunodeficiency virus (HIV), emergence of drug resistant M. tuberculosis, and failure to develop highly effective TB vaccines have limited control of the TB epidemic. Trained immunity is an enhanced innate immune response which functions independently of the adaptive/acquired immune system and responds non-specifically to reinfection with invading agents. Recently, several studies have found trained immunity has the capability to control and eliminate M. tuberculosis infection. Over the past decades, however, the consensus was adaptive immunity is the only protective mechanism by which hosts inhibit M. tuberculosis growth. Furthermore, autophagy plays an essential role in the development of trained immunity. Further investigation of trained immunity, M. tuberculosis infection, and the role of autophagy in this process provide a new possibilities for vaccine development. In this review, we present the general characteristics of trained immunity and autophagy. We additionally summarize several examples where initiation of trained immunity contributes to prevention of M. tuberculosis infection and propose future directions for research in this area.

Identification and validation of a T-cell-related MIR600HG/hsa-mir-21-5p competing endogenous RNA network in tuberculosis activation based on integrated bioinformatics approaches

“…Further in-depth exploration of the effect of HIV on TB activity was not within the scope of the current study. However, the five critical T-cell subsets and several gene biomarkers identified in the present study are also reportedly affected by HIV infection ( Jasenosky et al, 2015 ; Zhou et al, 2021 ). The results of the present study also suggest implications for future research on the molecular mechanisms by which HIV facilitates TB activity.…”

Hematopoietic stem cells are a reservoir for trained immunity in autoimmune disease

“…We generated BMDMs from mice treated ± pristane for eight weeks, and as controls we included BMDMs from mice treated for seven days with poly I:C (pIC), a double-stranded RNA analogue which induces IFN-I driven inflammation independently of an autoimmune process (Pichlmair and Reis e Sousa, 2007;Essers et al, 2009;Pietras et al, 2014). We then confirmed the generation of a highly pure BMDM population in each setting (Gutierrez et al, 2004;Kaufmann et al, 2018;Moorlag, Khan, et al, 2020;Zhou et al, 2021). Interestingly, BMDMs from mice treated with pristane or pIC had an increased ability to kill live M. avium based on qRT-PCR analysis of bacterial copy number after 72 hours (Fig 3B).…”

Does the trained immune system play an important role in the extreme longevity that is seen in the Sardinian blue zone?

“…Currently direct evidence for the induction of trained immunity by the encounter of virulent Mtb with innate immune cells is not available. However, it has been well documented that monocytes exposed to the attenuated Mtb strain Bacillus Calmette-Guérin (BCG) do undergo functional and epigenetic reprogramming characteristic of trained immunity ( Steigler et al, 2019 ; Ferluga et al, 2020 ; Kong et al, 2021 ; Zhou et al, 2021 ). Therefore, we consider it likely that, during tuberculosis, trained innate immune cells with a proinflammatory/maladaptive phenotype emerge.…”