| First Author | Weehuizen TA | Year | 2012 |
| Journal | Infect Immun | Volume | 80 |
| Issue | 5 | Pages | 1853-7 |
| PubMed ID | 22331429 | Mgi Jnum | J:182511 |
| Mgi Id | MGI:5315787 | Doi | 10.1128/IAI.05534-11 |
| Citation | Weehuizen TA, et al. (2012) Expression and Function of Transforming Growth Factor beta in Melioidosis. Infect Immun 80(5):1853-7 |
| abstractText | Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor beta (TGF-beta), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-beta expression and function in experimental melioidosis. TGF-beta expression was determined in 33 patients with culture-proven infection with B. pseudomallei and 30 healthy controls. We found that plasma TGF-beta concentrations were strongly elevated during melioidosis. In line with this finding, TGF-beta expression in C57BL/6 mice intranasally inoculated with B. pseudomallei was enhanced as well. To assess the role of TGF-beta, we inhibited TGF-beta using a selective murine TGF-beta antibody. Treatment of mice with anti-TGF-beta antibody resulted in decreased lung Smad2 phosphorylation. TGF-beta blockade appeared to be protective: mice treated with anti-TGF-beta antibody and subsequently infected with B. pseudomallei showed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-beta treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-beta treatment did not have an effect on survival. In conclusion, TGF-beta is upregulated during B. pseudomallei infection and plays a limited but proinflammatory role during experimental melioidosis. |
