Journal
ANNUAL REVIEW OF IMMUNOLOGY, VOL 39
Volume 39, Issue -, Pages 611-637Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-093019-010426
Keywords
Mycobacterium tuberculosis; innate immunity; macrophage; inflammation; cytokines; innate cells; PRRs; pattern recognition receptors
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Funding
- NSF Graduate Research Fellowships - National Institute of Allergy and Infectious Diseases
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Infection with Mycobacterium tuberculosis causes a significant number of deaths annually worldwide, where the role of innate immune cells and the inflammatory response in the infection process are crucial yet complex.Understanding the balance of cell-intrinsic control and inflammation regulation is essential for developing effective therapeutics and vaccines.
Infection with Mycobacterium tuberculosis causes >1.5 million deaths worldwide annually. Innate immune cells are the first to encounter M. tuberculosis, and their response dictates the course of infection. Dendritic cells (DCs) activate the adaptive response and determine its characteristics. Macrophages are responsible both for exerting cell-intrinsic antimicrobial control and for initiating and maintaining inflammation. The inflammatory response to M. tuberculosis infection is a double-edged sword. While cytokines such as TNF-alpha and IL-1 are important for protection, either excessive or insufficient cytokine production results in progressive disease. Furthermore, neutrophils-cells normally associated with control of bacterial infection-are emerging as key drivers of a hyperinflammatory response that results in host mortality. The roles of other innate cells, including natural killer cells and innate-like T cells, remain enigmatic. Understanding the nuances of both cell-intrinsic control of infection and regulation of inflammation will be crucial for the successful development of host-targeted therapeutics and vaccines.
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