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An anti-infective peptide that selectively modulates the innate immune response
Abstract
We show that an innate defense-regulator peptide (IDR-1) was protective in mouse models of infection with important Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Salmonella enterica serovar Typhimurium. When given from 48 h before to 6 h after infection, the peptide was effective by both local and systemic administration. Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses. To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously.
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“The reaction of neutrophils and macrophages during infection triggers the production of innate defence regulatory peptide 1 IDR1, with similar activity to defensins or cathelicidins [223].”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [223]
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1 of the 31 references couldn’t be matched to a known paper.
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- National Research Council Treating Infectious Diseases in a Microbial World: Report of Two Workshops. Washington, D.C.: The National Academies Press, (2005).
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Metadata
- Authors
- Scott, M. G., Dullaghan, E., Mookherjee, N., Glavas, N., Waldbrook, M., Thompson, A., Wang, A., Lee, K., Doria, S., Hamill, P., Yu, J. J., Li, Y., Donini, O., Guarna, M. M., Finlay, B. B., North, J. R., & Hancock, R. E. W.
- Affiliations
- City of Vancouver (CA)
- University of British Columbia (CA)
- Corresponding author
- Hancock, Robert E W
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2007-03-25
- Volume
- 25
- Issue
- 4
- Pages
- 465-472
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2040733257
- Cited by
- 403
- References
- 31
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 19 · 2023: 15 · 2022: 14 · 2021: 20 · 2020: 16 · 2019: 15 · 2018: 22 · 2017: 16 · 2016: 25 · 2015: 28 · 2014: 14 · 2013: 30 · 2012: 29
- FWCI
- 25.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Keywords
- monocytes, macrophages, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Salmonella typhimurium, Gram-positive pathogens, Gram-negative pathogens, inflammatory cytokines, MAPK signaling
- MeSH terms
- Animals, Anti-Infective Agents, Bacterial Infections, Disease Models, Animal, Gene Expression Regulation, Humans, Immunity, Innate, Inflammation, Lipopolysaccharides, Peptides, Treatment Outcome, Models, Immunological, Mice
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