# Bioactivities of pneumococcal cell wall in neuropathogenesis

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $448,750

## Abstract

Project Summary/Abstract
Using the pneumococcus as a model, our lab has revealed many features of the biochemical basis of the
inflammatory response to bacteria in the brain. How the pneumococcus traffics across the blood brain
barrier is shared by other meningeal pathogens. We determined how neurons die by apoptosis during
infection and revealed the role of cell wall/TLR2 in host damage. The important discovery of this
application is the opening of a new area of pathogenesis at the maternal/fetal interface that will inform
new aspects of cell wall/TLR2 effects in the brain. We have determined that cell wall, a universal
pathogen associated molecular pattern, circulates in the bloodstream of pregnant mice and traverses the
placenta to the fetal brain. The response of fetal neurons is not the well characterized inflammation and
neuronal death of the postnatal setting but the exact opposite: neuroproliferation without inflammation.
This response involves two new activities of cell wall: 1) induction of cell proliferation without
inflammatory signaling via TLR2, and 2) remodeling of embryonic brain anatomy and changes in
postnatal behavior. An understanding of the details of this new biology, to be investigated in this
application, represents both novel bacterial pathogenesis and an avenue of high potential for tangible
medical impact.
 We propose in Aim 1 to undertake detailed neuroanatomical assessment of the changes in brain
architecture and define the window of neuroproliferation in embryogenesis. In Aim 2 we will characterize
the signaling cascades initiated by cell wall to induce neuroproliferation, including via TLR2 and novel
sources of PI3 kinase and induction of the neuronal transcription factor FoxG1. This will link innate
immune receptors to nuclear transcription factors for the first time. Aim 3 will determine how cell wall
released during the treatment of maternal sepsis recapitulates the neuroproliferation seen in the model of
prenatal IV cell wall exposure of the mother. We will define the consequences to postnatal behavior of
prenatal neuroproliferation.

## Key facts

- **NIH application ID:** 9812834
- **Project number:** 5R01AI128756-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Elaine I Tuomanen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,750
- **Award type:** 5
- **Project period:** 2016-11-04 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9812834

## Citation

> US National Institutes of Health, RePORTER application 9812834, Bioactivities of pneumococcal cell wall in neuropathogenesis (5R01AI128756-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9812834. Licensed CC0.

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