# Complement and coagulation in B. anthracis peptidoglycan-induced sepsis

> **NIH NIH U19** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $456,075

## Abstract

Project Summary
Our work demonstrates that peptidoglycan (PGN), a major component of the cell wall of all Gram-positive
bacteria, promotes inflammation and coagulation. Baboons responded to in vivo PGN challenge with features
of systemic inflammation and disseminated intravascular coagulopathy (DIC) similar to those seen in patients
with inhalation anthrax. We found evidence of activation of both the intrinsic and extrinsic coagulation
pathways. In vitro, we found PGN stimulated robust cytokine production in human innate immune cells and
prothrombinase activity in human platelets exposed to highly purified polymeric PGN derived from B. anthracis
or Staphylococcus aureus. Innate immune cell responses required PGN recognition by surface Fcγ receptors,
phagocytosis, digestion in lysosomes, and stimulation of cytoplasmic NOD sensors. In the last iteration of this
grant, we showed that these processes were dependent on human serum opsonins, IgG and serum amyloid P.
We also showed that PGN-stimulated human monocytes expressed tissue factor (TF), an initiator of the
extrinsic coagulation pathway, in part by virtue of the proinflammatory cytokines.
This project will provide mechanistic insight into PGN-stimulated pathologies. First, we will test whether and
how the anthrax toxins affect the immune system activation events we have documented to date and listed
above. Second, we will identify the pathways that regulate PGN-induced activation of the intrinsic coagulation
pathway in vivo. Lastly, we will apply existing biological inhibitors to each pathway (intrinsic, extrinsic
coagulation and complement) to ask which of these contributes most to the pathology, organ failure and death
in PGN-challenged animals. The results will greatly inform treatment options for patients with Gram-positive
bacteremia.

## Key facts

- **NIH application ID:** 9927976
- **Project number:** 5U19AI062629-17
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Kenneth Mark Coggeshall
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,075
- **Award type:** 5
- **Project period:** 2004-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927976

## Citation

> US National Institutes of Health, RePORTER application 9927976, Complement and coagulation in B. anthracis peptidoglycan-induced sepsis (5U19AI062629-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927976. Licensed CC0.

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