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

The study titled “Suppressive Myeloid Cells in SARS-CoV-2 and Mycobacterium Tuberculosis Co-infection” presents a comprehensive analysis of the role played by myeloid-derived suppressor cells (MDSCs) in the co-infection of Tuberculosis (TB) and COVID-19. Published on 20th July 2023 by Jane Alexandra Shaw and colleagues, the research highlights the intricate relationship between the immune system, infectious diseases, and the impact of suppressive myeloid cells on disease outcomes.

Here’s a detailed summary:

Introduction

The study begins by acknowledging the high prevalence of TB and recent SARS-CoV-2 infections in certain regions, making acute or chronic co-infection or sequential infection with Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 inevitable. Epidemiological reports have shown that co-infection with Mtb and SARS-CoV-2 leads to worsened patient outcomes, with both active TB and previous TB increasing the risk of in-hospital mortality from COVID-19.

The Role of Suppressive Myeloid Cells

Suppressive myeloid cells, especially MDSCs, are critical in immune regulation and tolerance. They maintain the balance between healing and harm during the immune response by limiting excessive inflammation and preventing immune-mediated tissue damage. However, in pathological conditions like chronic inflammation, cancer, or extensive tissue trauma, the balance tips toward more harm. The study delves into the function of MDSCs in the pathophysiology of cancer and chronic infection, noting that these cells, which are of myeloid origin, acquire a pathological activation state in response to prolonged weak pro-inflammatory signals present in chronic infection or cancer.

MDSC in Tuberculosis

In TB, classically activated myeloid cells are the initial effectors of antimycobacterial responses. However, alternatively activated myeloid cell subsets, labeled as MDSCs, have less effective mycobactericidal activity, low expression of MHC class II, and secrete immune mediators that suppress T cell responses and promote lung damage. The study details how MDSCs are detected in blood, BALF, and pleural fluid of patients with active pulmonary and pleural TB disease and discusses their role in granuloma research, highlighting their accumulation at the edges of necrotic granulomas in the lung parenchyma of infected Mtb-susceptible mice, which is associated with TB disease progression and uncontrolled bacterial replication.

MDSC in COVID-19

Similar to TB and other viral infections, myeloid cells are the first responders to infection with SARS-CoV-2. However, a proportion of people infected with SARS-CoV-2 suffer a marked dysregulation of the innate immune response, especially the myeloid cell compartment. This dysregulated state is characterized by the emergence of immature neutrophils and monocytes with suppressive features, including MDSCs. High peripheral blood frequencies of both subsets of MDSCs in COVID-19 have been observed, particularly in severe and fatal disease. The study discusses the immunosuppressive abilities of these SARS-CoV-2-induced MDSCs and their role in the genesis of lung fibrosis in COVID-19 patients.

MDSC in SARS-CoV-2 and Mtb Co-infection

The study hypothesizes that pre-existing latent TB infection (LTBI) followed by SARS-CoV-2 infection is a likely scenario, given that a significant portion of the world’s population has been latently infected with Mtb. However, many patients present with a long history of symptoms and cavitary lung lesions at TB diagnosis, implying chronicity of disease, suggesting that a scenario of active TB disease followed by SARS-CoV-2 infection is also likely.

Conclusion and Implications

The study concludes that MDSCs play a potential role in determining the outcomes of Mtb/SARS-CoV-2 coinfection in all disease severities and iterations of the coinfection sequence. It highlights the need for more evidence to determine if MDSCs impact the outcome of SARS-CoV-2 infection in early TB or LTBI, the interactions relevant to vaccines, and if a host-directed therapy aimed at modulating the effect of MDSCs might improve the outcome of active TB disease/COVID-19 coinfection. The study calls for future research to address these critical questions and further our understanding of the complex interplay between these pathogens and the immune system.

By shedding light on the role of suppressive myeloid cells in co-infections, this study provides valuable insights that could lead to better clinical outcomes through targeted interventions and therapies. The comprehensive analysis presented in the study underscores the importance of understanding the immune system’s response to co-infection and the potential of MDSCs as a target for therapeutic intervention.

Read More: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1222911/full

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