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

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.

Automated summary

Epidemiologic data indicate that both current and previous tuberculosis (TB) increase the risk of in-hospital mortality from COVID-19, and a similar trend is observed for poor outcomes from Mtb infection after recent SARS-CoV-2. Dysregulation of immunity explains the dual risk posed by co-infection, with a dysfunctional innate immune response observed in COVID-19. Myeloid-derived suppressor cells (MDSC) play a crucial role in this process by becoming immunosuppressive and impairing pathogen clearance. MDSC are enriched in severe COVID-19 patients and are associated with higher levels of inflammatory cytokines.