# Pertussis inflammation is mediated by a balance between peptidoglycan recognition proteins-1 and -4

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $386,250

## Abstract

Project Summary
 Recent years have seen a re-emergence of pertussis as a major public health concern, despite
successful mass vaccination programs. Critical pertussis disease causes over 150,000 deaths annually.
Antibiotics are only effective if given before the onset of the characteristic cough. For these reasons, there is an
urgent need for the development of new treatments.
 The long-term goal of our group is to develop anti-pertussis therapeutics. Our central hypothesis is that
targeting tissue damage and inflammation induced by bacterial virulence factors will have a greater benefit than
traditional bactericidal therapies. We have demonstrated the potential of sphingosine-1-phosphate receptor
(S1PR) agonists in reducing pulmonary inflammation in mice and baboons. The objective of this work is to
understand the beneficial elements of the S1PR agonist-mediated response to guide the next generation of anti-
microbials. We identified two peptidoglycan recognition proteins (PGLYRP), -1, and -4 an antimicrobial protein,
as differentially regulated by S1PR agonism. PGLYRPs elicit bactericidal activity through interactions with
peptidoglycan (PGN). PGYLRP1 but not PGLYRP4 can stimulate inflammatory responses following PGN
binding. We hypothesize that PGLYRP4 competes with PGLYRP1 to mediate inflammatory responses. Further,
we propose that this is mediated by inhibition of host triggering receptor on myeloid cells 1 (TREM1).
 TREM-1 is an amplifier of inflammatory responses. It is upregulated following pattern recognition receptor
activation and its activity amplifies inflammatory cytokine expression. TREM-1 ligands include PGLYRP1-PGN
complexes. TREM-1 expression is reduced by S1PR agonism and inhibitor treated mice show reduced
inflammatory pathology following B. pertussis infection. We hypothesize that TREM-1 acts as a checkpoint
between beneficial bacterial control and detrimental inflammatory pathology.

## Key facts

- **NIH application ID:** 10416387
- **Project number:** 1R01AI167947-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Ciaran Skerry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,250
- **Award type:** 1
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10416387

## Citation

> US National Institutes of Health, RePORTER application 10416387, Pertussis inflammation is mediated by a balance between peptidoglycan recognition proteins-1 and -4 (1R01AI167947-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10416387. Licensed CC0.

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