Cited by 403Antimicrobial Peptides and ActivitiesImmune Response and InflammationSepsis Diagnosis and Treatment

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An anti-infective peptide that selectively modulates the innate immune response

Scott, Monisha G, Dullaghan, Edie, Mookherjee, Neeloffer, Glavas, Natalie, Waldbrook, Matthew, Thompson, Annick, Wang, Aikun, Lee, Ken, Doria, Silvana, Hamill, Pam, Yu, Jie Jessie, Li, Yuexin, Donini, Oreola, Guarna, M Marta, Finlay, B Brett, North, John R, Hancock, Robert E W·2007·Nature Biotechnology

DOI 10.1038/nbt1288

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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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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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Retracted
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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: Mookherjee, Neeloffer
Wang, Aikun
Lee, Ken
Yu, Jie Jessie
Li, Yuexin
Donini, Oreola
Guarna, M Marta
Finlay, B Brett
Hancock, Robert E W
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2007-03-25
Volume: 25
Issue: 4
Pages: 465-472
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt1288
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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An anti-infective peptide that selectively modulates the innate immune response

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