Tassili A F WeehuizenCatharina W. WielandGerritje J W van der WindtJan Willem DuitmanLouis BoonNicholas P J DaySharon J. PeacockTom van der PollW. Joost WiersingaAcademic Medical Centre, University of AmsterdamBioceros BVMahidol UniversityNuffield Department of Clinical MedicineUniversity of Cambridge2018-06-112018-06-112012-05-01Infection and Immunity. Vol.80, No.5 (2012), 1853-185710985522001995672-s2.0-84861122490https://repository.li.mahidol.ac.th/handle/123456789/14330Melioidosis, 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 factorβ (TGF-β), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-β expression and function in experimental melioidosis. TGF-β expression was determined in 33 patients with culture-proven infection with B. pseudomallei and 30 healthy controls. We found that plasma TGF-β concentrations were strongly elevated during melioidosis. In line with this finding, TGF-β expression in C57BL/6 mice intranasally inoculated with B. pseudomallei was enhanced as well. To assess the role of TGF-β, we inhibited TGF-β using a selective murine TGF-β antibody. Treatment of mice with anti-TGF-β antibody resulted in decreased lung Smad2 phosphorylation. TGF-β blockade appeared to be protective: mice treated with anti-TGF-β antibody and subsequently infected with B. pseudomallei showed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-β treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-β treatment did not have an effect on survival. In conclusion, TGF-β is upregulated during B. pseudomallei infection and plays a limited but proinflammatory role during experimental melioidosis. © 2012, American Society for Microbiology.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1128/IAI.05534-11