Innate Immune Defenses in Human Tuberculosis: An Overview of the Interactions betweenMycobacterium tuberculosisand Innate Immune Cells

Abstract

Tuberculosis (TB) remains a serious global public health problem that results in up to 2 million deaths each year. TB is caused by the human pathogen, Mycobacterium tuberculosis (Mtb), which infects primarily innate immune cells patrolling the lung. Innate immune cells serve as barometers of the immune response against Mtb infection by determining the inflammatory milieu in the lungs and promoting the generation of adaptive immune responses. However, innate immune cells are also potential niches for bacterial replication and are readily manipulated by Mtb. Our understanding of the early interactions between Mtb and innate immune cells is limited, especially in the context of human infection. This review will focus on Mtb interactions with human macrophages, dendritic cells, neutrophils, and NK cells and detail evidence that Mtb modulation of these cells negatively impacts Mtb-specific immune responses. Furthermore, this review will emphasize important innate immune pathways uncovered through human immunogenetic studies. Insights into the human innate immune response to Mtb infection are necessary for providing a rational basis for the augmentation of immune responses against Mtb infection, especially with respect to the generation of effective anti-TB immunotherapeutics and vaccines.

Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques

“…It is important to bear in mind that MHC-identical MCMs are not necessarily genetically identical outside the MHC, which may explain why our results contrast with the observation that monozygotic twin marmosets infected with the same strains of M. tuberculosis exhibited similar disease courses (36). In addition, the secretion of cytokines and presentation of antigens by macrophages, dendritic cells, or other innate cell types to initiate the adaptive immune response are well established to play a critical role in controlling M. tuberculosis replication and determining overall TB resistance (37)(38)(39). Ultimately, MHCmatched MCMs infected with the same dose and strain of M. tuberculosis may be valuable for defining non-MHC determinants of TB disease.…”

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages

“…Mtb can be recognized by numerous receptors and induces a network of signaling pathways to drive inflammatory responses, involving toll-like receptors (TLRs), C-type lectins, Aryl hydrocarbon receptor (AhR), and Cyclic GMP-AMP synthase (cGAS). [34][35][36] Studies on gene expression profiles of Mtbinfected human macrophages provided the evidence for the importance of IL-1b and IL-12 in combating Mtb. 37 Importantly, one study identified CCL1, produced from macrophages of TB patients after Mtb stimulation, was involved in host susceptibility to TB.…”

Heterogeneity in tuberculosis

“…These responses are an integral component of host defence and bacterial containment 34,43,44,61 , and they are intimately linked with granuloma outcome 37,62–64 . The particular immune cells involved in TB immunity 34,65–67 , and their localization and kinetics 32,41,61,68 , have been extensively reviewed in the past few years. Here, we discuss how the heterogeneity of the immune response in TB influences the local granuloma microenvironment.…”