Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 19;26(5):106629.
doi: 10.1016/j.isci.2023.106629. Epub 2023 Apr 8.

Mycobacterium tuberculosis and SARS-CoV-2 co-infections: The knowns and unknowns

Kim R Chiok  1 , Neeraj Dhar  1   2   3 , Arinjay Banerjee  1   3   4   5   6   7
Affiliations
Review

Mycobacterium tuberculosis and SARS-CoV-2 co-infections: The knowns and unknowns

Kim R Chiok et al. iScience. .

Abstract

Health impacts of Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 co-infections are not fully understood. Both pathogens modulate host responses and induce immunopathology with extensive lung damage. With a quarter of the world's population harboring latent TB, exploring the relationship between SARS-CoV-2 infection and its effect on the transition of Mtb from latent to active form is paramount to control this pathogen. The effects of active Mtb infection on establishment and severity of COVID-19 are also unknown, despite the ability of TB to orchestrate profound long-lasting immunopathologies in the lungs. Absence of mechanistic studies and co-infection models hinder the development of effective interventions to reduce the health impacts of SARS-CoV-2 and Mtb co-infection. Here, we highlight dysregulated immune responses induced by SARS-CoV-2 and Mtb, their potential interplay, and implications for co-infection in the lungs. As both pathogens master immunomodulation, we discuss relevant converging and diverging immune-related pathways underlying SARS-CoV-2 and Mtb co-infections.

Keywords: Bacteriology; Microbiology; Virology.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
SARS-CoV-2 and M. tuberculosis infection within the lung microenvironment SARS-CoV-2 infection induces cell death in lung epithelial cells (A). SARS-CoV-2 infection induces the release of pro-inflammatory cytokines and chemoattractants (B), which increases the influx of immune cells within the lung microenvironment (C). Infiltrated immune cells produce excessive pro-inflammatory mediators like TNF-α and IL-1, and antiviral type I IFN (D). M. tuberculosis (Mtb) can infect epithelial cells and macrophages within the lung environment (E). Mtb-infected macrophages secrete a subset of cytokines (F) that recruits immune cells and macrophages which communicate via IL-12 and IFNγ (G) to mount anti-Mtb responses (H). Mtb exploits the influx of macrophages to acquire new hosts, and in turn, amplify cytokine production (F and G). TB infections are characterized by formation of structured cellular aggregates called granulomas (I) where both pro- and anti-inflammatory responses co-exist and influence bacterial dynamics (J). While cytokine responses that are induced during monotypic infections are being studied, little is known about the combinatorial impact of SARS-CoV-2- and Mtb-mediated induction of cytokine responses on host tissue health and the respective pathogens (K and L). Figure created with BioRender.com.
Figure 2
Figure 2
Non-inflammatory and pro-inflammatory cell death in SARS-CoV-2 and M. tuberculosis infection SARS-CoV-2 viral and M. tuberculosis (Mtb) promote non-inflammatory apoptosis (A), pro-inflammatory necroptosis (B), and pyroptosis (C) modes of cell death through viral and bacterial proteins and cell membrane damage. The combinatorial effects of cell death modes on SARS-CoV-2 and Mtb dynamics are not well understood. Whether apoptosis influences SARS-CoV-2 is still an open question, although it likely restricts Mtb replication and spread (D). Mtb exploits necroptotic cells to enhance its replication, but the necroptotic microenvironment may not be suitable for SARS-CoV-2 (E). The impact of pyroptosis on both pathogens, if any, has not been defined, albeit both pathogens can elicit pyroptosis in respiratory tissue (F). Nevertheless, the ensuing cytokine release as by-product of pro-inflammatory cell death contributes to lung injury (G). Figure created with BioRender.com.
Figure 3
Figure 3
Therapeutic intervention strategies for SARS-CoV-2 and M. tuberculosis Both SARS-CoV-2 and M. tuberculosis (Mtb) infections induce the expression of type I IFNs and pro-inflammatory mediators. However, cytokine identity and levels during co-infection remain less studied. Indeed, the crosstalk between infection-induced cytokines, and its impact on SARS-CoV-2 infection, active TB, and latent TB remain less known. Multiple antiviral compounds have shown promising efficacy against SARS-CoV-2 (A). Similarly, effective antibiotics exist for both active and latent forms of Mtb infection (B). Clinical trials for immune modulators, cytokine blockers, and anti-inflammatory compounds have shown promise in mitigating infection-induced immunopathology, but the collective effect of these drugs on lung tissue homeostasis, pathogen control, and infection resolution during co-infection remains unknown (C). Figure created with BioRender.com.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. World Health Organization . Annual Global TB Report of WHO; 2022. Annual Report of Tuberculosis. 1–68.
    1. Diedrich C.R., Flynn J.L. HIV-1/Mycobacterium tuberculosis coinfection immunology: how does HIV-1 exacerbate tuberculosis? Infect. Immun. 2011;79:1407–1417. doi: 10.1128/IAI.01126-10. - DOI - PMC - PubMed
    1. Esmail H., Riou C., Bruyn E.d., Lai R.P.-J., Harley Y.X.R., Meintjes G., Wilkinson K.A., Wilkinson R.J. The immune response to Mycobacterium tuberculosis in HIV-1-Coinfected persons. Annu. Rev. Immunol. 2018;36:603–638. doi: 10.1146/annurev-immunol-042617-053420. - DOI - PubMed
    1. Walaza S., Cohen C., Tempia S., Moyes J., Nguweneza A., Madhi S.A., McMorrow M., Cohen A.L. Influenza and tuberculosis co-infection: a systematic review. Influenza Other Respir. Viruses. 2020;14:77–91. doi: 10.1111/irv.12670. - DOI - PMC - PubMed
    1. Mhimbira F., Hiza H., Mbuba E., Hella J., Kamwela L., Sasamalo M., Ticlla M., Said K., Mhalu G., Chiryamkubi M., et al. Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study. Clin. Microbiol. Infection. 2019;25:107–107.e7. doi: 10.1016/j.cmi.2018.03.019. - DOI - PMC - PubMed