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Cathelicidins protect mice from Bacillus anthracis spore challenge through their lytic and immunomodulatory abilities
Author(s) -
Lisanby Mark,
Swiecki Melissa,
Pflughoeft Kathryn,
Koehler Theresa,
Kearney John
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.859.9
Subject(s) - cathelicidin , bacillus anthracis , lytic cycle , microbiology and biotechnology , bacilli , biology , antimicrobial peptides , spore , aerosolization , antimicrobial , immunology , bacteria , virus , genetics , anatomy , inhalation
Cathelicidins are a family of antimicrobial peptides that are expressed in mammals and possess lytic and immunomodulatory properties. In this study, we determined the minimum effective concentration of cathelicidins from three different species against B. anthracis bacilli using standard radial diffusion and microbroth dilution assays. The effects of each peptide on spore germination and vegetative outgrowth were determined with microscopic and flow cytometric analyses. While no peptide prevented germination, one cathelicidin arrested outgrowth by directly lysing the plasma membrane of the developing bacilli. Cathelicidin administration protected C57BL/6 mice during subcutaneous spore challenge but failed to protect A/J mice from pulmonary infection. Cellular recruitment and depletion studies showed that the protection in C57BL/6 mice resulted from the direct lysis of germinated spores as well as the increased recruitment of Mac‐1 + /Gr‐1 + cells to the injection site. These findings suggest that cathelicidins might be utilized to augment the initial innate immune response to B. anthracis spore exposure and inhibit disease progression. This work was supported by grants from the National Institutes of Health: AI057699‐03 to J.F.K, and AI057156 and AI33537 to T.M.K. M.W.L was supported by T32AI55438 and K.J.P was supported by T32AI055449.