# Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $1,391,820

## Abstract

PROJECT SUMMARY/ABSTRACT
Approximately one-fourth of the world's population is latently infected (LTBI) with Mycobacterium tuberculosis
(Mtb) and those infected have a 10% lifetime risk of developing clinical pulmonary TB (PTB) disease over their
lifetime. Global efforts to combat TB are hampered by the emergence of extensively drug-resistant and multidrug-
resistant strains and the variable efficacy of the currently available vaccine, M. bovis Bacille Calmette Guerin.
Unfortunately, the immune mechanisms that govern progression from LTBI to PTB are poorly defined, preventing
rational design of treatments or vaccines that stimulate immune control of TB. Thus, there is an urgent need to
better understand the immune parameters that contribute to Mtb control. The tubercle granuloma is a hallmark
of TB and is important for the immune control of Mtb infection. However, not all granulomas effectively control
TB, as they are seen both during LTBI and during TB reactivation (TB-R) and PTB. During the previous R01
funding period, we used human TB samples and non-human primate (NHP) and mouse models of TB to
demonstrate an unequivocal protective role for inducible bronchus-associated lymphoid tissue (iBALT)
containing clearly defined B-cell follicles during both primary and vaccine-induced responses to Mtb infection.
Additionally, we determined that a dominant feature of granulomas during PTB is the accumulation of neutrophils
that produce proinflammatory molecules such as S100A8/A9 proteins and limit iBALT formation. Our long-term
goal is to develop clinical strategies to restrain Mtb growth and prevent progression from LTBI to TB disease.
Based on work from this funded R01, the objective of this R01 renewal is to identify the roles of granuloma-
associated B cells and neutrophils in TB infection and disease progression and to determine if iBALT is an
effective target for preventing TB progression. Towards this overall goal, we propose to use both small animal
and large animal models to address the following specific aims: In Specific Aim 1 we will investigate the role of
iBALT-residing B cells in protecting against TB; In Specific Aim 2, we will evaluate the role of neutrophilic
proteins such as S100A8/A9 in limiting iBALT during PTB, and to determine if targeting S100A8/A9 pathways
will reduce TB disease and improve Mtb control; Finally, in Specific Aim 3, we will determine if iBALT structures
can be targeted to prevent TB progression in Mtb-infected hosts. The knowledge to be gained from these studies
is significant, as it will directly advance the development of new therapeutics and vaccine strategies for limiting
TB-R and progression to TB.

## Key facts

- **NIH application ID:** 10223661
- **Project number:** 2R01AI111914-06A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Deepak Kaushal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,391,820
- **Award type:** 2
- **Project period:** 2015-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223661

## Citation

> US National Institutes of Health, RePORTER application 10223661, Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis (2R01AI111914-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10223661. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*