# Tuberculosis Immunopathogenesis During Superinfection with SARS-CoV2

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $751,882

## Abstract

An estimated 1/3 of the world population is already infected with Mycobacterium tuberculosis
(M. tb), the causative agent of tuberculosis (TB), with an almost 5-10% of latent infected patients
developing active tuberculosis during their lifetime. In the last three years, infection with severe
acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2, a.k.a. SCV2) the causative agent of
COVID-19, has resulted in 6.5 million deaths. According to the WHO Global TB Report 2022,
the SCV2 pandemic in 2020-2021 was associated with the reversal of the steady decline in TB
death rate for the first time since 2005. Our long-term goal is to better control tuberculosis and
manage cases of superinfection with SCV2 as well as gain insight to immunological consequences
of SCV2 infection. Preliminary data from our group indicated SCV2 superinfection increased M.
tb loads in murine lungs and promoted dissemination to extra-pulmonary organs, which was
associated with specific changes in immunomodulatory cytokines (e.g., IFN-g and IL10) and
decreased general inflammation in the lungs. These data underpinned our central hypothesis that
SCV2 superinfection compromises anti-TB immunity, leading to greater dissemination of M. tb.
To address the central hypothesis we plan to I) Characterize the TB/SCV2 superinfection in a
latent murine model of TB using C3HeB/FeJ mice in a setup termed Immune Competent TB Model
(ICTM); II) Define mechanisms of M. tb dissemination during SCV2 superinfection by targeting
IFN-g and IL-10 cytokines using reporter and repletion murine models that are infected with M. tb
before superinfection with SCV2 BA.5. Finally, III) Examine M. tb progression in Diversity
Outbred (DO) mouse model compared to inbred mice to characterize mycobacterial growth phase
associated with pathological and immunological changes during TB/SCV2 superinfection.
 Outcomes from this project will further improve our understanding of TB immunopathogenesis
and how latent infections in humans can convert to active cases of TB including furthering
knowledge on the granuloma’s role in containment and pathogenesis. Importantly, gained
knowledge could help in understanding TB immunopathogenesis during any future respiratory
superinfection, not SCV2 alone. Future research building on outcomes from this project could
help in the control of both TB and COVID-19 pandemics that could be tailored for other respiratory
emerging infections (e.g. Influenza).

## Key facts

- **NIH application ID:** 10841608
- **Project number:** 5R01AI173411-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ADEL M TALAAT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $751,882
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841608

## Citation

> US National Institutes of Health, RePORTER application 10841608, Tuberculosis Immunopathogenesis During Superinfection with SARS-CoV2 (5R01AI173411-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10841608. Licensed CC0.

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