Suppressive myeloid cells in SARS-CoV-2 and Mycobacterium tuberculosis co-infection

Abstract

Epidemiologic data show that both current and previous tuberculosis (TB) increase the risk of in-hospital mortality from coronavirus disease-2019 (COVID-19), and there is a similar trend for poor outcomes from Mycobacterium tuberculosis (Mtb) infection after recent SARS-CoV-2. A shared dysregulation of immunity explains the dual risk posed by co-infection, but the specific mechanisms are being explored. While initial attention focused on T cell immunity, more comprehensive analyses revealed a dysfunctional innate immune response in COVID-19, characterized by reduced numbers of dendritic cells, NK cells and a redistribution of mononuclear phagocytes towards intermediate myeloid subsets. During hyper- or chronic inflammatory processes, activation signals from molecules such as growth factors and alarmins lead to the expansion of an immature population of myeloid cells called myeloid-deprived suppressor cells (MDSC). These cells enter a state of pathological activation, lose their ability to rapidly clear pathogens, and instead become broadly immunosuppressive. MDSC are enriched in the peripheral blood of patients with severe COVID-19; associated with mortality; and with higher levels of inflammatory cytokines. In TB, MDSC have been implicated in loss of control of Mtb in the granuloma and ineffective innate and T cell immunity to the pathogen. Considering that innate immune sensing serves as first line of both anti-bacterial and anti-viral defence mechanisms, we propose MDSC as a crucial mechanism for the adverse clinical trajectories of TB-COVID-19 coinfection.

Myeloid-derived suppressor cells in pleural effusion as a diagnostic marker for early discrimination of pulmonary tuberculosis from pneumonia

“…This exacerbates disease progression and contributes to the observed differences in discriminatory ability between TPE and PPE. Furthermore, the distinct immunosuppressive characteristics of PMN-MDSCs, including their capacity to inhibit T cell proliferation and cytokine production, have significant implications for the immunopathogenesis of TPE and the clinical outcomes in patients with TPE and PPE (35,(40)(41)(42).…”

Inflammatory immune profiles associated with disease severity in pulmonary tuberculosis patients with moderate to severe clinical TB or anemia

“…It is a common notion that lost immune control in TB is characterized by excess production of pro-inflammatory cytokines together with Th1 and Th17 cytokines, which result in neutrophil infiltration and bystander action of T cells that promote pathological inflammation and tissue destruction at the site of infection in the lung (46,47). While this is true in many aspects, poor immune control in TB has also been shown to be dictated by premature expansion of anti-inflammatory macrophages or myeloid-derived suppressor cells (MDSC) as well as regulatory B and T cells (Breg and Treg) that emerge as a result of chronic inflammation (10,48,49). This is particularly evident in granulomatous lesions at the site of Mtb infection, where numerous recent reports from humans and non-human primates demonstrate that dysfunctional Th1/Th17 CD4+ and cytolytic CD8+ T cells responses correlate with bacterial growth and disease progression, while type 2 immunity as well as FoxP3+ Tregs and MDSCs expressing inhibitory molecules and mediators are associated with bacterial persistence (50)(51)(52)(53)(54)(55)(56).…”