# Cytomegalovirus as a risk factor for exacerbation of Mycobacterium tuberculosis infection

> **NIH NIH R21** · COLORADO STATE UNIVERSITY · 2021 · $39,793

## Abstract

SUMMARY
Mycobacterium tuberculosis is a worldwide public health problem, and the need to develop new vaccines to
prevent further deaths is critical. However, vaccine development is hindered by the difficulty of translating pre-
clinical animal model data to human trials. There may be multiple factors associated with the difference in
outcomes between pre-clinical and clinical settings. Of significant interest is the role that co-infections play in
mediating immunity to M. tuberculosis infection and how these co-infections increase the risk of developing
tuberculosis disease. Co-infections, such as with human Cytomegalovirus virus (HCMV), are important drivers
of immune activation in HIV, particularly in sub-Saharan Africa. HCMV associated immune activation in the HIV
exposed is known to drive CD4+ T cell decline, hasten immuno-senescence and lead to eventual immune
exhaustion. There also emerging evidence to support the fact that HCMV plays a significant role in exacerbating
tuberculosis disease in immunocompetent individuals, thus it is important to investigate the interaction between
these pathogens and how they mediate the immunity. The current proposal is designed to develop an in vivo
experimental co-infection in mice with M. tuberculosis and Cytomegalovirus and with M. tuberculosis. Thus the
primary focus of this application is to develop a mouse model to investigate the role of co-infection in the
immune mechanisms required to kill M. tuberculosis, and once these have been identified can we start to
understand better how to make effective TB vaccines. We will focus on cytomegalovirus co-infection during M.
tuberculosis infection to determine how it contributes to exacerbation of TB disease using a mouse model. We
will develop the model to understand innate and adaptive immune responses during co-infection (Aim 1), test
the hypothesis that excessive reactive species contribute to TB disease using a Type I interferon independent
mechanism (Aim 2) and determine how infection with each pathogen interacts with neighboring cells and
determine if CMV infection of macrophages and dendritic cells skews development of macrophages towards
an M2 or suppressive phenotype resulting in poor adaptive immunity to M. tuberculosis in-vitro. (Aim 3). These
studies will provide the basis for future model development to identify mechanisms that may interfere with the
efficacy of new and existing anti-tuberculosis vaccines.

## Key facts

- **NIH application ID:** 10136517
- **Project number:** 5R21AI146442-02
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** ANGELO A IZZO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,793
- **Award type:** 5
- **Project period:** 2020-04-01 → 2021-04-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136517

## Citation

> US National Institutes of Health, RePORTER application 10136517, Cytomegalovirus as a risk factor for exacerbation of Mycobacterium tuberculosis infection (5R21AI146442-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10136517. Licensed CC0.

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