# Myeloid-derived suppressor cells modulate disease severity in children with viral lower respiratory tract infections

> **NIH NIH K23** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2024 · $180,199

## Abstract

Project Summary
Severe lower respiratory tract infection (LRTI) due to viral pathogens remains one of the most common causes
of death for young children worldwide. Current management of patients with viral-induced LRTI focuses on
supportive care, but outcomes may be improved by augmenting the host immune response to fight the virus and
regain immune homeostasis. A growing body of literature suggests that children with severe viral LRTI have an
impaired adaptive immune response, specifically decreased T cell proliferation and cytokine production. Myeloid-
derived suppressor cells (MDSC) are a heterogeneous cell population that expand during inflammatory
conditions and potently inhibit T cell proliferation and function. MDSC have been extensively studied in adult
oncologic populations where clinical trials show promising results of improved outcomes by inhibiting MDSC as
part of chemotherapy and anti-tumor vaccine treatment regimens. Our group has identified significant increases
in the frequency of MDSC populations in children with septic shock and COVID-19 and demonstrated
associations between increased percentages of MDSC and worse clinical outcomes. However, it is unknown
what role MDSC play in children with viral-induced severe LRTI. The overall goal of this proposal is to identify
MDSC as contributors to the immune response in children with viral LRTI and identify mechanistic pathways as
potential therapeutic targets for future investigations. Our central hypothesis is that increased frequency of
MDSC will be associated with worse clinical outcomes and decreased numbers of CD4+ and CD8+ T
cells in children with viral LRTI, and that pediatric MDSC-induced T cell suppression is reversible
through inhibition of the PD-1 pathway. The proposed experiments will involve blood sampling of children
with PCR-confirmed viral LRTI to characterize the dynamics of MDSC and lymphocyte populations during
hospitalization. We will also use our in vitro model of MDSC induced from pediatric peripheral blood mononuclear
cells and select patient samples to establish the PD-1 pathway as an important mechanism of MDSC-mediated
inhibition of T cell proliferation and cytokine production in children. This career development award will generate
the necessary data to inform the design of future studies of the pediatric immune response in severe lower
respiratory tract infections and will equip me with the necessary tools to achieve independence as a patient-
oriented clinician-scientist.

## Key facts

- **NIH application ID:** 10984694
- **Project number:** 1K23HL171862-01A1
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Katherine Bline
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $180,199
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984694

## Citation

> US National Institutes of Health, RePORTER application 10984694, Myeloid-derived suppressor cells modulate disease severity in children with viral lower respiratory tract infections (1K23HL171862-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10984694. Licensed CC0.

---

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