The double-edged sword of Tregs in M tuberculosis, M avium, and M absessus infection

Abstract

Immunity against different Mycobacteria species targeting the lung requires distinctly different pulmonary immune responses for bacterial clearance. Many parameters of acquired and regulatory immune responses differ quantitatively and qualitatively from immunity during infection with Mycobacteria species. Nontuberculosis Mycobacteria species (NTM) Mycobacterium avium- (M avium), Mycobacterium abscessus-(M abscessus), and the Mycobacteria species Mycobacterium tuberculosis-(Mtb). Herein, we discuss the potential implications of acquired and regulatory immune responses in the context of animal and human studies, as well as future directions for efforts to treat Mycobacteria diseases.

Keywords: Mycobacterium abscessus; Mycobacterium avium; Mycobacterium tuberculosis; Immunity.

Figure 1.. Regulatory T cell suppression of antigen-presenting cells (APC).

CTLA-4 on Treg cells’ surface can prevent or depress the up-regulation of CD80 and CD86, the major costimulatory molecules on APC. LAG-3 on Treg cells can interact with MHC class II on APC by binding LAG-3 to MHC class II molecules on immature DCs, causing an inhibitory signal that suppresses DC maturation and immaturity. Tissue destruction results in extracellular ATP that functions as an indicator and exerts inflammatory effects on DCs. Catalytic inactivation of extracellular ATP by CD39 represents an anti-inflammatory mechanism that may be used by Treg cells to prevent the harmful effects of ATP on antigen-presenting cell function. In contrast, Nrp-1 (neuropilin) promotes extended interactions between Treg cells and immature DCs and limits access of the effector cells to APC.

Figure 2.

Host defense defects causing M. tuberculosis exist less frequently than in NTM while immunocompetent individuals readily succumb to M. tuberculosis infection. However, disseminated NTM disease and the determinants of susceptibility to NTM pulmonary disease are better understood. Host factors implicated in increased susceptibility include structural lung abnormalities, genetic disorders affecting mucociliary clearance, and use of steroids or other immunomodulatory drugs, such as TNF-α blockers.