# Cellular and Molecular Mechanisms of Fungal Sepsis in the Critically Ill Patient

> **NIH NIH R01** · EAST TENNESSEE STATE UNIVERSITY · 2021 · $288,600

## Abstract

Abstract
Invasive infections caused by opportunistic fungi are increasingly common in the surgical ICU.
The mortality rate for fungal sepsis in the ICU patient is 30-40%. It is well accepted that aging
plays a critical role in the incidence of sepsis and age is a known independent predictor of
mortality in sepsis. Fungal infections have become an increasing problem in older ICU patients.
This is due, in part, to the fact that sepsis results in immune suppression. However, it is also
known that healthy aged adults show senescence of immune function. In addition, aging
patients frequently have multiple co-morbidities and undergo more invasive procedures leading
to a higher risk of sepsis. The underlying cellular and molecular mechanisms that result in
increased susceptibility to fungal infection in the aged and/or septic patient are not fully
understood. The research outlined in this application is focused on addressing that deficit in our
knowledge. We have acquired preliminary data which demonstrate that healthy aged
individuals (>60 y.o.) show decreased anti-fungal Th17 mediated responses when compared to
young healthy controls. We also have preliminary data which indicate that clinical sepsis
decreases leukocyte expression of Dectin-1, the primary pattern recognition receptor for
induction of anti-fungal innate immunity. Based on these data and the published literature we
hypothesize that “susceptibility to fungal sepsis in the aged critically ill patient is mediated by
specific cellular and molecular defects in anti-fungal innate immunity”. To test our hypothesis we
propose the three following specific aims. In aim 1 we will identify the age related defects in
Dectin-1/Th17 dependent signaling in human leukocytes from healthy adults >60 y.o. We will
examine Dectin-1/Th17 mediated intracellular signaling in response to Candida albicans or C.
albicans cell wall glucan in leukocytes from adults >60 y.o. and compare them to those from
adults <30 y.o. In aim 2 we will identify defects in Dectin-1/Th17 dependent signaling in
leukocytes from patients with sepsis. In this aim we will critically evaluate Dectin-1/Th17
mediated signaling in response to Candida albicans or glucan in leukocytes from septic patients
and compare them to age matched healthy adults. In aim 3 we will investigate the impact of
clinical sepsis on human leukocyte Dectin-1 expression. We will correlate Dectin-1 expression
with the type of infection, acute physiology scores and injury indices, length of hospital stay,
days in ICU and survival outcome. These experiments will provide new knowledge of the
mechanisms that render the aged critically ill patient susceptible to life threatening fungal
infections. In addition, we will acquire new clinical data that may identify novel predictors of
susceptibility to fungal infection. Finally, we will investigate strategies to increase resistance to
opportunistic fungal infections in the critically ill patient.

## Key facts

- **NIH application ID:** 10142491
- **Project number:** 5R01GM122934-05
- **Recipient organization:** EAST TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Tammy Regena Ozment
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $288,600
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142491

## Citation

> US National Institutes of Health, RePORTER application 10142491, Cellular and Molecular Mechanisms of Fungal Sepsis in the Critically Ill Patient (5R01GM122934-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10142491. Licensed CC0.

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