Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia

Abstract

Tuberculous meningitis (TBM) is the most severe complication of tuberculosis (TB) and is associated with high rates of disability and mortality. Mycobacterium tuberculosis (M. tb), the infectious agent of TB, disseminates from the respiratory epithelium, breaks through the blood-brain barrier, and establishes a primary infection in the meninges. Microglia are the core of the immune network in the central nervous system (CNS) and interact with glial cells and neurons to fight against harmful pathogens and maintain homeostasis in the brain through pleiotropic functions. However, M. tb directly infects microglia and resides in them as the primary host for bacillus infections. Largely, microglial activation slows disease progression. The non-productive inflammatory response that initiates the secretion of pro-inflammatory cytokines and chemokines may be neurotoxic and aggravate tissue injuries based on damages caused by M. tb. Host-directed therapy (HDT) is an emerging strategy for modulating host immune responses against diverse diseases. Recent studies have shown that HDT can control neuroinflammation in TBM and act as an adjunct therapy to antibiotic treatment. In this review, we discuss the diverse roles of microglia in TBM and potential host-directed TB therapies that target microglia to treat TBM. We also discuss the limitations of applying each HDT and suggest a course of action for the near future.

LRRC25 Inhibits IFN-γ Secretion by Microglia to Negatively Regulate Anti-Tuberculosis Immunity in Mice

“…Upon Mtb invasion, the activated microglia release numerous cytokines and chemokines, contributing to the defense against central nervous system infection and neurogenesis-related pathogenesis [13,14]. Activated microglia differentiate into M1 (pro-inflammatory phenotype) and secrete pro-inflammatory cytokines, including IFN-γ, TNF-α/β, and IL-1α/β [15,16], as confirmed in the pneumococcal meningitis animal models [17,18]. However, excessive activation can elicit a nonspecific immune response and damage the nerve tissue [19].…”

Nanoscale Glutathione-Functionalized Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Loaded with Metformin for the Treatment of Spinal Cord Injury

“…SCI is a CNS disease with high incidence, high disability rate, and very low cure rate, which is mainly caused by falling from high places and car accidents. , SCI mainly includes primary injury caused by mechanical injury and secondary injury caused by various pathological processes. , At present, inhibiting the overexpression of CNS proinflammatory factors caused by secondary injury is considered as one of the main ways to treat SCI. − It has been reported that after SCI, overexpression of pro-inflammatory factors and oxidative stress in the injured microenvironment will further aggravate neurotoxicity at the injured site . Therefore, inhibiting the expression of inflammatory factors at the injured site and reducing the degree of oxidative stress have become the focus of this study.…”

“…24−26 It has been reported that after SCI, overexpression of pro-inflammatory factors and oxidative stress in the injured microenvironment will further aggravate neurotoxicity at the injured site. 66 Therefore, inhibiting the expression of inflammatory factors at the injured site and reducing the degree of oxidative stress have become the focus of this study.…”