Advances in the study of myeloid-derived suppressor cells in infectious lung diseases

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells capable of inhibiting T-cell responses. MDSCs have a crucial role in the regulation of the immune response of the body to pathogens, especially in inflammatory response and pathogenesis during anti-infection. Pathogens such as bacteria and viruses use MDSCs as their infectious targets, and even some pathogens may exploit the inhibitory activity of MDSCs to enhance pathogen persistence and chronic infection of the host. Recent researches have revealed the pathogenic significance of MDSCs in pathogens such as bacteria and viruses, despite the fact that the majority of studies on MDSCs have focused on tumor immune evasion. With the increased prevalence of viral respiratory infections, the resurgence of classical tuberculosis, and the advent of medication resistance in common bacterial pneumonia, research on MDSCs in these illnesses is intensifying. The purpose of this work is to provide new avenues for treatment approaches to pulmonary infectious disorders by outlining the mechanism of action of MDSCs as a biomarker and therapeutic target in pulmonary infectious diseases.

Myeloid-derived suppressor cells in influenza virus-induced asthma exacerbation

“…In line with those findings, we found that long-term HDM exposure, as was used in the models in this study, increased both the number as well as the immunosuppressive activity of PMN- and M-MDSCs in the lung. Akin to the findings in murine asthma models, pulmonary viral infections, triggered by viruses such as influenza, have been reported to induce expansion of immunosuppressive pulmonary MDSCs in mice ( 10 , 18 ). In the asthma exacerbation model used in this study, long-term exposure to HDM was combined with a one-time exposure to IAV.…”

“…An increasing body of evidence suggests that MDSCs play a crucial role in lung diseases such as lung cancer, chronic obstructive pulmonary disorder (COPD), tuberculosis, pulmonary hypertension, cystic fibrosis, pulmonary infection, and asthma ( 7 , 10 ). Our previous findings further underlined the important role of MDSCs in murine models of asthma ( 12 , 13 ).…”

“…These findings may hint at complex temporal patterns of the MDSC response in relation to the model of asthma exacerbation. While the increase in MDSC number is likely a result of enhanced recruitment of MDSCs to the lung, the changes in MDSC activity may be directly related to changes in the micro-environment of the lungs, such as those induced by rapid alterations in cytokine production, following IAV infection ( 7 , 8 , 10 , 18 ). The observed increase of IL-4 and IL-13 in the BALF of asthmatic mice suggests a local increase in MDSC activity, as both cytokines have been shown to induce MDSC activation ( 8 ).…”

“…MDSCs are a heterogenous group of immature myeloid cells with potent immunosuppressive capacity ( 8 ). Since their discovery in cancer patients, they have been found to play a role in numerous diseases encompassing inflammation, infection, and autoimmunity ( 7 – 10 ). MDSCs are subdivided into polymorphonuclear (PMN-) and monocytic (M-) MDSCs, which are characterized by CD11b + Ly6G + Ly6C int and CD11b + Ly6G-Ly6C hi in mice, and CD11b + CD14 - CD15 + and CD11b + CD14 + HLA - DR -/lo CD15 - in humans, respectively ( 8 , 11 ).…”

Mycobacterium tuberculosis: Pathogenesis and therapeutic targets

“…In fact, elevated levels of MDSCs have been observed in both blood and sputum of patients with active TB in studies, 338 and have also been induced in healthy individuals after exposure to Mtb 339 . These cells play a detrimental role in diminishing protective T‐cell responses and may contribute to the inability of hosts to eradicate the infection, which subsequently leads to the development of TB disease 340 . Tasquinimod, 341 an experimental quinoline‐3‐carboxamide, has demonstrated tremendous promise in inhibiting tumor growth in murine cancer models and has recently been shown to deplete MDSCs and reduce the relative bacterial burden in the lung and spleen of murine models of TB 342 (Table 2).…”