# The Role of Group 3 Innate Lymphoid cells (ILC3) in Tuberculosis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $117,308

## Abstract

Abstract
Over the past three months, COVID-19 has emerged as a major pandemic with over ~ 1.9 million productive
infections and ~100,000 deaths due to infection with the novel Coronavirus SARS-CoV-2, a viral pathogen
which is highly infectious and pathogenic. This is particularly true in the elderly and people with
immunocompromising conditions who are exhibiting acute respiratory distress syndrome at a greater
frequency. Unfortunately, no known cures and vaccines exist. Worse, there were no well-characterized animal
models of SARS-CoV-2 infection and COVID-19 disease till recently. With the limited information on host
innate immune responses, early reports implicate a role for inflammation in mediating COVID-19 disease. As
an logical extension of ongoing work on innate immune responses in the lung on the parent grant, we
hypothesize that similar to tuberculosis (TB), control of SARS-CoV2 will correlate with accumulation of innate
lymphoid cells including NK cells in the lung, while inflammation and increased disease will be associated with
myeloid cell accumulation. To test this hypothesis, we will utilize recently acquired banked lung samples from a
novel rhesus macaque model of SARS-CoV-2 infection/COVID-19 disease developed at the SouthWest
National Primate Research Center (in collaboration with Deepak Kaushal Lab, Co-I on parent grant). These
new results from the NHP model indicate that rhesus macaques develop signs of human COVID-19 disease
including pyrexia, dysregulation of complete blood cell counts indicative of viral infection, acute stress markers,
and experience cough and weight-loss. This is accompanied by high viral loads in bronchoalveolar lavage
(BAL) and lungs, and pneumonia is detected by CT scan as well as grossly at necropsy. Single cell RNA
sequencing (scRNA-seq) is just beginning to be applied to the immune system in animal models and humans
in both healthy and diseased states. The application of scRNA-seq to COVID-19 samples from macaques is
particularly well-suited, as the immune cells infiltrating the lung that may play roles in the disease are diverse,
including virtually all types of lymphocytes (ILCs, CD4+ T cells, CD8+ T cells, γδ T cells, NK cells, B cells) and
several myeloid cell types (monocytes, macrophages and potentially dendritic cells (DCs) and neutrophils
(PMNs)). Within each of these subtypes, further heterogeneity exists in terms of cytokine production and
transcription factor expression, such that each subtype may demonstrate further heterogeneity. Because
scRNA-seq can define the transcriptomic heterogeneity of a complex community of cells and assign unbiased
identity classifications to cell populations, it is optimally suited for application to the study of complex
inflammatory disease such as TB and COVID-19. The data obtained and its computational analysis will
delineate the nature of inflammation, especially the role of innate cells such as NK cells and ILCs in COVID-19
mediated inflammation. These ...

## Key facts

- **NIH application ID:** 10146615
- **Project number:** 3R01AI134236-03S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** MARCO COLONNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $117,308
- **Award type:** 3
- **Project period:** 2020-05-22 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146615

## Citation

> US National Institutes of Health, RePORTER application 10146615, The Role of Group 3 Innate Lymphoid cells (ILC3) in Tuberculosis (3R01AI134236-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10146615. Licensed CC0.

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