# Mechanisms of itch and neural regulation of inflammation in S. aureus infection

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $29,035

## Abstract

Project Summary
Staphylococcus aureus is a major human pathogen that causes epicutaneous and subcutaneous skin
infections. Evidence shows that S. aureus could be a key contributor to chronic itch conditions, including atopic
dermatitis (AD), where over 90% of sufferers are colonized by S. aureus. We hypothesize S. aureus directly
activates pruriceptor neurons, the itch-mediating sensory neurons densely innervating the epidermis, during
epicutaneous skin infections. In turn, this exacerbates and promotes not only itch, but also skin inflammation
and disease pathology in AD. Sensory neuron activation and the subsequent release of neuropeptides cause
neurogenic inflammation, resulting in the recruitment/activation of immune cells. The main objective of this
proposal is to determine the mechanisms of itch during S. aureus epicutaneous infection and the contribution
of sensory neurons in driving inflammation and skin pathology. In Specific Aim 1, we will establish a mouse
model of epicutaneous S. aureus infection where chronic itch behavior can be quantified. Nerve sprouting and
nerve density into the epidermis, key components of AD, will also be analyzed. I have recently shown S.
aureus pore-forming toxins (PFTs), such as alpha hemolysin (Hla), are capable of activating sensory neurons.
Several recent studies using this model of infection have pointed to the key role of PSMαs, a class of S.
aureus PFTs, in inflammation. We have obtained isogenic mutant strains of bacteria lacking these toxins and
will test if the specific PFTs, Hla and PSMαs, contribute to itch-behavior in vivo. In Specific Aim 2, we will
determine whether these sensory neurons mediate inflammation and host-defense during an epicutaneous S.
aureus infection. Sensory neurons will be depleted using chemical and transgenic strategies. Trpv1 expressing
neurons will be depleted using resiniferatoxin and by using the transgenic mouse line, Trpv1-Cre/Dta. In
addition, to target a different, but overlapping set of sensory neurons, the transgenic mouse line Nav1.8-
cre/Dta will be used. In these strategies, the subsequent consequences on immune cell recruitment, bacterial
clearance, and skin pathology will be determined. The proposed research is novel given the poor mechanistic
understanding of pathogen-induced itch, particularly in S. aureus infection. The results will not only fill a critical
gap in our knowledge of direct interactions of S. aureus with sensory neurons to drive itch, but also pioneer
studies determining the role of the nervous system in driving inflammation in the skin. Therapeutic strategies
targeting these newfound bacterial-neuron interactions can be developed as novel treatments to alleviate both
AD pathology and its debilitating itch, especially in conjunction with S. aureus infection.

## Key facts

- **NIH application ID:** 9827479
- **Project number:** 5F31AI138384-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Kimbria J Blake
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $29,035
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9827479

## Citation

> US National Institutes of Health, RePORTER application 9827479, Mechanisms of itch and neural regulation of inflammation in S. aureus infection (5F31AI138384-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9827479. Licensed CC0.

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