Revisiting the role of mesenchymal stem cells in tuberculosis and other infectious diseases

Abstract

Mesenchymal stem cells (MSCs) play diverse roles ranging from regeneration and wound healing to immune signaling. Recent investigations have indicated the crucial role of these multipotent stem cells in regulating various aspects of the immune system. MSCs express unique signaling molecules and secrete various soluble factors that play critical roles in modulating and shaping immune responses, and in some other cases, MSCs can also exert direct antimicrobial effects, thereby helping with the eradication of invading organisms. Recently, it has been demonstrated that MSCs are recruited at the periphery of the granuloma containing Mycobacterium tuberculosis and exert “Janus”-like functions by harboring pathogens and mediating host protective immune responses. This leads to the establishment of a dynamic balance between the host and the pathogen. MSCs function through various immunomodulatory factors such as nitric oxide (NO), IDO, and immunosuppressive cytokines. Recently, our group has shown that M.tb uses MSCs as a niche to evade host protective immune surveillance mechanisms and establish dormancy. MSCs also express a large number of ABC efflux pumps; therefore, dormant M.tb residing in MSCs are exposed to a suboptimal dose of drugs. Therefore, it is highly likely that drug resistance is coupled with dormancy and originates within MSCs. In this review, we discussed various immunomodulatory properties of MSCs, their interactions with important immune cells, and soluble factors. We also discussed the possible roles of MSCs in the outcome of multiple infections and in shaping the immune system, which may provide insight into therapeutic approaches using these cells in different infection models.

Whole blood vs serum-derived exosomes for host and pathogen-specific tuberculosis biomarker identification: RNA-seq based machine learning approach

“…Therefore, pluripotent stem cells might play a role in the longterm persistence of Mtb during dormancy and are capable of migrating and differentiating into various cell types, contributing to the dissemination of the infection. In addition, MSCs are also involved in the formation of granuloma during the latent stage by creating a favorable microenvironment for dormant Mtb bacilli and inhibiting the T-cell function facilitating the survival of latent bacteria (Devi et al 2023). The erythropoietin-producing hepatocellular carcinoma (Eph) receptors and their corresponding ephrin ligands are a family of proteins involved in cell signaling and are known to play essential roles in various cellular processes, including cell migration and tissue development (Darling and Lamb 2019).…”

Management Challenges of Extrapulmonary Nontuberculous Mycobacterial Infection: A Single-Center Case Series and Literature Review

“…Therefore, bedaquiline can be regarded as a host-directed therapy for bacterial infections. Additionally, there is a recently published article revisiting the idea of using specifically mesenchymal stem cell infusion in patients with mycobacterial infection with a successful effect to treat MDR TB infection as a hostdirected therapy [43]. The immunomodulatory effects of stem cells and their involvement in various infectious diseases result from their interactions with different immune cells in the body, such as T cells, B cells, macrophages, dendritic cells, and NK cells.…”

“…There is little knowledge of the interactions of stem cells with different immune cells within the granuloma, which is a major obstacle to understanding their persistence. These types of stem cells may also be a potentially interesting therapeutic approach for different infections due to their potential to interact with the immune system [43].…”

“…The limited number of NTM experimental models investigating host modulation and HDT emphasizes the need and urgency to understand NTM pathogenesis as well as identify potentially relevant host targets [43].…”