# Tri-Institutional TB Research Unit: Persistence and Latency

> **NIH NIH U19** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $6,446,187

## Abstract

Mycobacterium tuberculosis (Mtb) is one of the world's most successful pathogens. WHO estimates that
about one third of the world's population has a positive skin test that reflects a long-term adaptive immune
response to Mtb antigens. These individuals are considered to have actual or potential latent Mtb infection
(LTBl). Among them, a minority that cannot be identified prospectively will develop reactivation tuberculosis
(TB) despite having apparently normal immunity. Active TB can be contagious both to those who were
previously unexposed and those with LTBl and is usually lethal if untreated. Adequate numbers of CD4 T
cells, tumor necrosis factor alpha (TNFα), and interferon-gamma (IFNy) are validated determinants of control
of primary TB, but the vast majority of HIV negative patients with reactivation TB do not have defined defects
in these pathways. The ability of Mtb to remain latent within the human host, and the related failure of the
human immune system to sterilize Mtb in latently infected individuals, are poorly understood. Antimicrobial
therapy for active infection by drug-sensitive Mtb is effective, but current drugs must be given for 6 months to
achieve relapse-free cure rates of >95%. The necessity for this prolonged duration of therapy is attributable
to the ability of genetically drug-sensitive Mtb to adopt a phenotypically drug-tolerant, persistent state in
which it is not readily sterilized by current drugs. Despite substantial efforts to understand these two critical
features of Mtb infection—latency and persistence—fundamental questions remain about the genetic,
immunologic, and microbiologic contributors to both. We seek to close this knowledge gap through a
Tuberculosis Research Unit (TBRU) that unites investigators at Weill Cornell Medical College (WCMC),
Rockefeller University (RU), and Memorial Sloan Kettering Cancer Center (MSKCC), with selected external
collaborators, and draws on patients at the WMC-affiliated GHESKIO Centres in Haiti to provide insight into
latency and persistence of Mtb during human infection.

## Key facts

- **NIH application ID:** 9970379
- **Project number:** 5U19AI111143-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Michael S Glickman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $6,446,187
- **Award type:** 5
- **Project period:** 2014-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970379

## Citation

> US National Institutes of Health, RePORTER application 9970379, Tri-Institutional TB Research Unit: Persistence and Latency (5U19AI111143-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9970379. Licensed CC0.

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