# Cellular and molecular mechanisms controlling sepsis-induced immunoparalyses state

> **NIH NIH R35** · UNIVERSITY OF IOWA · 2024 · $385,226

## Abstract

Project Summary/Abstract
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It
represents a significant public health burden striking 1.7 million American annually (with 20-25% mortality). In
general, early stages of sepsis are characterized by a potentially detrimental hyperinflammatory state.
However, patients who survive the cytokine storm phase of sepsis enter a state of immunoparalysis defined by
enhanced susceptibility to infection, viral reactivation, and mortality years after the septic insult. Sepsis-induced
lymphopenia reduces the number of immune cells and influences the function of remaining/surviving cells.
Yet, the sepsis-induced lymphopenia is transient while the prolonged immunoparalysis (or
immunosuppression) that develops (even after lymphocyte numbers normalize) is now considered a leading
reason for the extended period of increased susceptibility to bacterial and viral pathogens normally handled by
the immune system in healthy individuals. Therefore, our long-term goal is to precisely determine, on cellular
and molecular levels, sepsis-induced changes in various lymphocyte populations that support and define the
chronic state of immunoparalysis and inability of immune cells to exert their effector functions properly. We
identified four interconnected areas of research that we will pursue: a) Explore molecular mechanisms that
govern long-term maintenance and function of infection-or vaccine-induced protective memory CD8 T cell
responses after sepsis; b) Define the cellular basis of increased susceptibility to tumor development and
decreased ability to evoke autoimmune responses in sepsis survivors; c) Develop new experimental models of
sepsis research; d) Investigate the interplay between clinical (human) and experimental (mouse) research to
elucidate mechanisms and pathways that control sepsis-induced immunoparalysis state. Addressing these key
gaps in our understanding of sepsis-induced immunoparalysis will ultimately uncover new targets that can be
used to develop better and more efficient treatments of sepsis survivors.

## Key facts

- **NIH application ID:** 10765664
- **Project number:** 5R35GM134880-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** VLADIMIR P BADOVINAC
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,226
- **Award type:** 5
- **Project period:** 2020-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765664

## Citation

> US National Institutes of Health, RePORTER application 10765664, Cellular and molecular mechanisms controlling sepsis-induced immunoparalyses state (5R35GM134880-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10765664. Licensed CC0.

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