Evasion of Innate and Adaptive Immunity byMycobacterium tuberculosis

Abstract

Through thousands of years of reciprocal coevolution, Mycobacterium tuberculosis has become one of humanity's most successful pathogens, acquiring the ability to establish latent or progressive infection and persist even in the presence of a fully functioning immune system. The ability of M. tuberculosis to avoid immune-mediated clearance is likely to reflect a highly evolved and coordinated program of immune evasion strategies that interfere with both innate and adaptive immunity. These include the manipulation of their phagosomal environment within host macrophages, the selective avoidance or engagement of pattern recognition receptors, modulation of host cytokine production, and the manipulation of antigen presentation to prevent or alter the quality of T-cell responses. In this article we review an extensive array of published studies that have begun to unravel the sophisticated program of specific mechanisms that enable M. tuberculosis and other pathogenic mycobacteria to persist and replicate in the face of considerable immunological pressure from their hosts. Unraveling the mechanisms by which M. tuberculosis evades or modulates host immune function is likely to be of major importance for the development of more effective new vaccines and targeted immunotherapy against tuberculosis.

Targeting Innate-Like T Cells in Tuberculosis

“…In vivo , MAIT cell accumulation in the primary infected lung tissue starts less than 10 days post BCG infection, as detected by an MR1-tetramer for measuring the frequency of MAIT cells isolated from bronchoalveolar lavage fluid (BALF) and lung tissue (33). Taking into account the slow growing curve and immune-escaping mechanism mediated by M. tuberculosis as discussed (2, 76), the kinetics of MAIT cell responses is essentially faster than the response of conventional CD8 + T cells in the lung infection of M. tuberculosis (Figure 1A). It appears that both the in vitro and in vivo kinetics of MAIT cells upon mycobacterial infection can be considered to resemble that of conventional memory T cells (33, 88).…”

“…Using a skin test, immune responses can be detected 5–6 weeks after M. tuberculosis infection in humans (74). In a drastic contrast to fast T cell responses to other intracellular bacteria, such as Listeria infection in mouse spleen (75), a much slower kinetics of T cell responses in M. tuberculosis infection may attribute to a slower growing curve of M. tuberculosis , bacterial inhibition of migratory activity, bacterial modulation of host antigen-presenting cells, and relatively immunoprivileged nature of the healthy alveolar tissues (2, 76). The antigen stimulation for conventional T cell activation occurs faster in vitro than in vivo because sufficient antigen presentation is usually warranted when setting up cell culture.…”

IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

“…M. tuberculosis employs several strategies to modulate effector CD4 T cell response (43). Several recent reports have indicated that PD-1–PD-L1/PD-L2 axis has a pivotal role in the regulation of T cell response to M. tuberculosis (29, 31, 33).…”

Mechanisms of M. tuberculosis Immune Evasion as Challenges to TB Vaccine Design

“…For each of these, M. tuberculosis has evolved the ability to inhibit or resist these defense mechanisms (Cambier et al, 2014; Goldberg et al, 2014). There is also increasing knowledge of “unconventional” or donor-unrestricted T cells (e.g., those with TCRs that interact with nonpolymorphic antigen-presenting molecules), including mycobacterial lipid antigen-specific T cells restricted by CD1a, CD1b, or CD1c (Van Rhijn and Moody, 2015), mucosal-associated invariant T cells (MAITs) (Gold et al, 2015), and γδ T cells.…”