Characterization of the murine macrophage response to infection with virulent and avirulent Burkholderia species

BMC Microbiology

Research Article

Jason T. Ladner¹  Mark J. Wolcott²  Melanie P. Ulrich³  Ricky L. Ulrich⁴  Rekha G. Panchal⁵  Chih-Yuan Chiang⁵  Jenifer F. Ojeda⁵  Tara A. Kenny⁵  Brett Eaton⁵  Douglas J. Lane⁵  Sina Bavari⁵  Samuel P. Dickson⁶  Rahul Raychaudhuri⁷  Mei Sun⁷  Kathleen Kuehl⁷  Krishna P. Kota⁸  David Covell⁹ 

[1] Center for Genome Sciences, USAMRIID, Fort Detrick, MD, USA;Diagnostic Systems Division, USAMRIID, Fort Detrick, MD, USA;Florida SouthWestern State College, Fort Myers, FL, USA;Institute for Therapeutic Innovation, Department of Medicine, University of Florida, Orlando, FL, USA;Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA;Office of Regulated Studies, USAMRIID, Fort Detrick, MD, USA;Pathology Division, USAMRIID, Fort Detrick, MD, USA;Perkin Elmer, Waltham, MA, USA;Screening Technologies Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick, MD, USA;

关键词: Burkholderia thailandensis;    Burkholderia mallei;    Burkholderia pseudomallei;    Burkholderia oklahomensis;    host response;   

DOI  :  10.1186/s12866-015-0593-3

 received in 2015-03-26, accepted in 2015-10-28,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundBurkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease – from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered.ResultsThe goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt.ConclusionsThese results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.

【 授权许可】

CC BY   
© Chiang et al. 2015