# Investigating platelets in the innate immune response to tuberculosis

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $160,738

## Abstract

PROJECT SUMMARY
 One-third of the world's population are infected with the bacterium that causes tuberculosis (TB), and ~10.4
million people develop disease each year and 1.3 million die. In pulmonary TB, the collagenase MMP-1 is the
primary effector of lung tissue destruction and cavity formation. Platelets may contribute to the MMP-mediated
tissue degrading phenotype seen in TB, as they recruit MMP-secreting leucocytes, upregulate leucocyte MMP
secretion, and secrete MMPs themselves, and they may be involved both in inflammation and the control of its
resolution. There is a growing interest in developing host-directed therapies that modify the immune response
to TB, with the aim of limiting inflammation and enhancing the effectiveness of existing anti-TB drugs. For this,
a detailed understanding of TB immunopathology is vital.
 We propose to investigate platelet activity in TB patients by correlating changes in markers of platelet
activation with measures of tissue destruction and clinical/radiological outcomes, focusing on markers
identified through our in vitro work and RNASeq. Our overarching hypothesis is that platelets regulate the
innate immune response to TB.
Hypothesis 1: Platelet activation and activity are increased in TB-infected individuals.
Specific Aim 1: To investigate the relationship between platelet activity and tissue destruction in newly
diagnosed patients with pulmonary TB compared to healthy controls and to individuals with non-TB
respiratory disease (symptomatic controls).
Specific Aim 2: To investigate dynamic changes in platelet activity in TB patients during treatment.
Hypothesis 2: Specific platelet-leukocyte signalling pathways will be differentially utilised in TB patients
compared to healthy controls and to patients with non-TB respiratory disease.
 Specific Aim 3: Signalling pathways that are identified using RNASeq and/or cellular experiments as
important in platelet-leukocyte interactions will be investigated in patients with TB by measuring downstream
associated mediators in blood and BALF. Pathways that may be therapeutically interrupted will be identified for
further investigation as potential targets for a host directed therapy.
 We believe that platelets are an important but neglected component of TB immunopathology. We anticipate
that we will find significant differences in platelet activity and activation in TB patients compared to patients with
non-TB pulmonary disease and healthy controls. We also expect that this will correlate with disease severity at
diagnosis and with loss of lung function at completion of treatment, and will improve with treatment.
 This study will provide novel information and will highlight potential targets for modification via a host-
directed therapy, which will be evaluated in an intervention study in the future.

## Key facts

- **NIH application ID:** 10009269
- **Project number:** 5R21AI142419-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ROBERT H GILMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,738
- **Award type:** 5
- **Project period:** 2019-09-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009269

## Citation

> US National Institutes of Health, RePORTER application 10009269, Investigating platelets in the innate immune response to tuberculosis (5R21AI142419-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10009269. Licensed CC0.

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