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

Abstract

Acinetobacter 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 50 μg of c-di-GMP administered 18 h 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.

• Authors: Lisa Zhao, Rhonda KuoLee, Greg Harris, Kha Tram, Hongbin Yan, Wangxue Chen
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 11 Issue 9 Pg. 1378-83 (Sep 2011) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 21496497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Chemical References

• Ccl2 protein, mouse
• Ccl3 protein, mouse
• Ccl5 protein, mouse
• Chemokine CCL2
• Chemokine CCL3
• Chemokine CCL5
• Chemokine CXCL2
• Chemokines
• Cxcl2 protein, mouse
• bis(3',5')-cyclic diguanylic acid
• Cyclic GMP

Topics

• Acinetobacter Infections (drug therapy, metabolism, microbiology, prevention & control)
• Acinetobacter baumannii (drug effects)
• Administration, Intranasal (methods)
• Animals
• Chemokine CCL2 (metabolism)
• Chemokine CCL3 (metabolism)
• Chemokine CCL5 (metabolism)
• Chemokine CXCL2 (metabolism)
• Chemokines (metabolism)
• Cyclic GMP (analogs & derivatives, pharmacology)
• Female
• Lung (drug effects, metabolism, microbiology, pathology)
• Mice
• Mice, Inbred C57BL
• Neutrophil Infiltration (drug effects)
• Time Factors