Exploring the Use of Medicinal Plants and Their Bioactive Derivatives as Alveolar NLRP3 Inflammasome Regulators during Mycobacterium tuberculosis Infection

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a successful intracellular pathogen that is responsible for the highest mortality rate among diseases caused by bacterial infections. During early interaction with the host innate cells, M. tuberculosis cell surface antigens interact with Toll like receptor 4 (TLR4) to activate the nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3 (NLRP3) canonical, and non-canonical inflammasome pathways. NLRP3 inflammasome activation in the alveoli has been reported to contribute to the early inflammatory response that is needed for an effective anti-TB response through production of pro-inflammatory cytokines, including those of the Interleukin 1 (IL1) family. However, overstimulation of the alveolar NLRP3 inflammasomes can induce excessive inflammation that is pathological to the host. Several studies have explored the use of medicinal plants and/or their active derivatives to inhibit excessive stimulation of the inflammasomes and its associated factors, thus reducing immunopathological response in the host. This review describes the molecular mechanism of the NLRP3 inflammasome activation in the alveoli during M. tuberculosis infection. Furthermore, the mechanisms of inflammasome inhibition using medicinal plant and their derivatives will also be explored, thus offering a novel perspective on the alternative control strategies of M. tuberculosis-induced immunopathology.

Keywords: Mycobacterium tuberculosis; NLRP3 inflammasomes; alveolar macrophages; immunopathology; interleukin 1 cytokines; medicinal plant derivatives; medicinal plants; pulmonary epithelial cells.

Figure 1

Overview of the alveolar NLRP3 inflammasome activation on alveolar innate cells during M. tuberculosis infection. The host PRRs (TLR4) is activated by M. tuberculosis surface PAMPs stimulate the NF-kB transcriptional factor to transcribe IL1, IL18, and CASP4/11 that are processed by activation of the inflammasome complex through NLRP3 and CASP1. Image was created in BioRender.com (accessed on 23 August 2021).

Figure 2

Medicinal plant and/or bioactive regulators of the NLRP3 inflammasome that can be exploited as immunomodulatory host-directed adjuvants during M. tuberculosis infection. Compounds denoted with * were tested in vivo. Image was created in BioRender.com (accessed on 23 August 2021).