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

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

Research output: Contribution to journalArticlepeer-review

287 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)465-472
Number of pages8
JournalNature Biotechnology
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 2007

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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