Abstract
Mycobacterium tuberculosis, the causative agent of tuberculosis, has infected humans for millennia. M. tuberculosis is well adapted to establish infection, persist in the face of the host immune response and be transmitted to uninfected individuals. Its ability to complete this infection cycle depends on it both evading and taking advantage of host immune responses. The outcome of M. tuberculosis infection is often a state of equilibrium characterized by immunological control and bacterial persistence. Recent data have highlighted the diverse cell populations that respond to M. tuberculosis infection and the dynamic changes in the cellular and intracellular niches of M. tuberculosis during the course of infection. M. tuberculosis possesses an arsenal of protein and lipid effectors that influence macrophage functions and inflammatory responses; however, our understanding of the role that specific bacterial virulence factors play in the context of diverse cellular reservoirs and distinct infection stages is limited. In this Review, we discuss immune evasion and provocation by M. tuberculosis during its infection cycle and describe how a more detailed molecular understanding is crucial to enable the development of novel host-directed therapies, disease biomarkers and effective vaccines.
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Acknowledgements
This work was funded by the US National Institutes of Health (R01 AI087682, R01 AI130454, R21 AI155380 and R21 AI160386 to J.A.P.; F31 AI152321 to S.J.G.). The authors thank members of the Philips laboratory for helpful discussions.
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J.A.P. conceived the Review; P.C. and S.J.G. contributed substantially to discussion of the content; P.C., S.J.G. and J.A.P. contributed equally to writing and editing the manuscript.
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Nature Reviews Microbiology thanks Samuel Behar; Volker Briken, who co-reviewed with Shivangi Rastogi; and Maziar Divangahi for their contribution to the peer review of this work.
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Glossary
- Cavitary lung disease
-
A pathological process in the lungs that results in gas-filled spaces, which are typically thick-walled and arise in areas of consolidation, mass or nodule.
- Inflammageing
-
Age-associated chronic, sterile and low-grade inflammation that leads to disease exacerbation.
- Opsonization
-
The coating of microorganisms by components of the immune system such as antibodies and complement proteins to facilitate their uptake and elimination by phagocytes.
- Clodronate
-
A bisphosphonate that, when encapsulated in liposomes, is preferentially taken up by macrophages, where it accumulates and causes cell death.
- Myelopoiesis
-
The process in which mature myeloid cells such as macrophages and neutrophils differentiate from myeloid progenitors that arise from haematopoietic stem cells.
- Atherosclerosis
-
A disease of arteries that is characterized by deposition of plaque, which is composed of fats, cholesterol and lipid-laden macrophages, on the artery wall.
- Paucibacillary disease
-
Tuberculosis with such a low number of bacilli that they are not apparent on smear microscopy.
- Metformin
-
A medication that is used to treat type 2 diabetes mellitus and that is being evaluated as a host-directed therapy for tuberculosis.
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Chandra, P., Grigsby, S.J. & Philips, J.A. Immune evasion and provocation by Mycobacterium tuberculosis. Nat Rev Microbiol 20, 750–766 (2022). https://doi.org/10.1038/s41579-022-00763-4
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DOI: https://doi.org/10.1038/s41579-022-00763-4