c-di-GMP protects against intranasal Acinetobacter baumannii infection in mice by chemokine induction and enhanced neurtrophil recruitment

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DOIResolve DOI: http://doi.org/10.1016/j.intimp.2011.03.024
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TypeArticle
Journal titleInternational Immunopharmacology
Volume11
Issue9
Pages13781383; # of pages: 6
Subjectacinetobacter baumannii; c-di-GMP; mice; neutrophils; pneumonia
AbstractAcinetobacter baumannii has emerged as a major cause of both community-associated and nosocomial infections worldwide. A. baumannii rapidly develops resistance to multiple antibiotics; as a result, infections by this pathogen have become increasingly difficult to treat. In this study, we evaluated the effect of 3',5'-cyclic diguanylic acid (c-di-GMP), a bacterial second messenger and immunomodulator, in the host defense against A. baumannii infection in a mouse model of intranasal infection. Our results showed that 50μg of c-di-GMP administered 18h prior to infection provided the best protection against intranasal infection with A. baumannii. Mechanistically, administration of c-di-GMP induced the production of chemokines KC, MCP-1, MIP-1α, MIP-2 and RANTES, and enhanced neutrophil recruitment in the lung. Moreover, depletion of neutrophils abolished the protective role of c-di-GMP. Taken together, our data suggest that c-di-GMP confers resistance against intranasal A. baumannii infection in mice through a neutrophil-dependent mechanism and that c-di-GMP should be further explored as an immunomodulator for the treatment of A. baumannii infection.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number19258795
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Record identifierbf2e0a90-b0a9-413e-970a-423537182383
Record created2012-03-08
Record modified2016-05-09
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