# Human anti-viral immune responses in tissues and circulation

> **NIH NIH U19** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $2,394,560

## Abstract

Program Summary
Studies of human immune responses to viruses and other pathogens have focused, by necessity, on sampling
of peripheral blood; however, innate and adaptive immune responses are initiated, function and maintained in
diverse tissue sites. Innate cells, including tissue macrophages and dendritic cells (DC) that encounter
pathogens at key entry points (e.g., lungs, intestines) do not appear in circulation. Similarly T cells infiltrate
infection sites and can persist as non-circulating tissue-resident memory T cells, which provide protective
responses in situ. At present, our understanding of tissue-localized innate and adaptive immune responses is
based on mouse models, and we lack fundamental knowledge on how innate and adaptive cells are organized
and function in human tissues. The overall goal of this research program in human immunity is to obtain in-
depth profiles of how human innate and adaptive immune cells in tissues respond to viral infection, with a focus
on the globally pervasive herpesvirus, Cytomegalovirus (CMV). CMV establishes lifelong persistence in
multiple sites, has broad effects on aging and immunity, and can be reactivated during immunosuppression in
transplantation and cancer, causing serious disease and mortality. The proposed research program, consisting
of three projects, and five cores, will obtain in-depth profiles of human immune cells involved in controlling
CMV in human tissue sites using our unique tissue resource where lymphoid, mucosal and peripheral tissue
are obtained from individual organ donors, compared to blood responses from living cohorts with active
infection. Project 1 (PL: Farber) will study T cell responses to CMV in tissues and circulation from organ donors
and transplant patients; Project 2 (PI: B. Reizis) will study how DC subsets in different sites functionally
respond to CMV and CMV-infected cells from both tissues and cohorts of transplant patients; and Project 3 (PI:
M. Merad) will profile macrophages in tissues and their responses to innate stimuli through TLR agonists and
CMV, and effect of CMV infection on macrophage function. The administrative core will coordinate organization
and financial aspects of the program, the Clinical Core will provide all samples including tissues from organ
donors and blood samples from transplant cohorts to the three projects. The Transcriptomics (RNAseq) and
single cell core (Core A) will provide high throughput RNA sequencing on the population and single cell level,
and multidimensional proteome profiling using cytometry by time-of-flight (CyTOF). The Viral assays core
(Core B) will measure CMV persistence in different tissue sites to dissect how virus persistence impacts
tissues immune responses. The data management and analysis core (DMAC) will store, curate and analyze all
data outputs from the projects and cores, apply bioinformatics for analysis of transcriptomic and proteomic
data, generate models to integrate the datasets, and submit raw dat...

## Key facts

- **NIH application ID:** 10074512
- **Project number:** 5U19AI128949-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Donna L. Farber
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,394,560
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-03-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074512

## Citation

> US National Institutes of Health, RePORTER application 10074512, Human anti-viral immune responses in tissues and circulation (5U19AI128949-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074512. Licensed CC0.

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