Abstract
Tuberculosis (TB) is still an important global threat and although the causing organism has been discovered long ago, effective prevention strategies are lacking. Mycobacterium tuberculosis (MTB) is a unique pathogen with a complex host interaction. Understanding the immune responses upon infection with MTB is crucial for the development of new vaccination strategies and therapeutic targets for TB. Recently, it has been proposed that sensing bacterial nucleic acid in antigen-presenting cells via intracellular pattern recognition receptors (PRRs) is a central mechanism for initiating an effective host immune response. Here, we summarize key findings of the impact of mycobacterial RNA sensing for innate and adaptive host immunity after MTB infection, with emphasis on endosomal toll-like receptors (TLRs) and cytosolic sensors such as NLRP3 and RLRs, modulating T-cell differentiation through IL-12, IL-21, and type I interferons. Ultimately, these immunological pathways may impact immune memory and TB vaccine efficacy. The novel findings described here may change our current understanding of the host response to MTB and potentially impact clinical research, as well as future vaccination design. In this review, the current state of the art is summarized, and an outlook is given on how progress can be made.
Highlights
The tremendous increase in life expectancy of today compared to a century ago is in large part attributable to the unraveling of infectious diseases pathology followed by the development of successful prevention and treatment options against particular pathogens [1]
It is known that human TLR8 activation inhibits expression of TLR7 and TLR9 in human embryonal kidney (HEK) cells and in human monocytes, though in tissue macrophages the potential of synergy has been proposed [37]
Another role for TLR3 as a target of mycobacterial virulence factors was recently suggested by mice studies, which revealed that Mycobacterium tuberculosis (MTB) inhibits the activation of TLR3 via c-ABL-dependent regulation of bone morphogenesis protein (BMP) [42]
Summary
The tremendous increase in life expectancy of today compared to a century ago is in large part attributable to the unraveling of infectious diseases pathology followed by the development of successful prevention and treatment options against particular pathogens [1]. Both antibiotic therapy and vaccination concepts are based on profound knowledge about the biology of the pathogen and its interaction with the host. We summarize recent findings on mycobacterial RNA recognition and its subsequent modulation of the host immune response through the induced cytokines IL-12, IL-21, and type I interferons, with its potential impact on TB vaccine development
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