Assessment of antimicrobial peptide LL-37 as a post-exposure therapy to protect against respiratory tularemia in mice

作者：Flick Smith Helen C^*; Fox Marc A; Hamblin Karleigh A; Richards Mark I; Jenner Dominic C; Laws Thomas R; Phelps Amanda L; Taylor Christopher; Harding Sarah V; Ulaeto David O; Atkins Helen S

来源：Peptides, 2013, 43: 96-101.

DOI：10.1016/j.peptides.2013.02.024

• Antimicrobial peptide
• LL-37
• Francisella tularensis LVS
• Mice

Early activation of the innate immune response is important for protection against infection with Francisella tularensis live vaccine strain (LVS) in mice. The human cathelicidin antimicrobial peptide LL-37 is known to have immunomodulatory properties, and therefore exogenously administered LL-37 may be suitable as an early post-exposure therapy to protect against LVS infection. LL-37 has been evaluated for immunostimulatory activity in uninfected mice and for activity against LVS in macrophage assays and protective efficacy when administered post-challenge in a mouse model of respiratory tularemia. Increased levels of pro-inflammatory cytokine IL-6, chemokines monocyte chemoattractant protein 1 (MCP-1) and CXCL1 with increased neutrophil influx into the lungs were observed in uninfected mice after intranasal administration of LL-37. Following LVS challenge, LL-37 administration resulted in increased IL-6, IL-12 p70, IFN gamma and MCP-1 production, a slowing of LVS growth in the lung, and a significant extension of mean time to death compared to control mice. However, protection was transient, with the LL-37 treated mice eventually succumbing to infection. As this short course of nasally delivered LL-37 was moderately effective at overcoming the immunosuppressive effects of LVS infection this suggests that a more sustained treatment regimen may be an effective therapy against this pathogen.

• 出版日期2013-5