TY - JOUR
T1 - Expression and Function of Transforming Growth Factor beta in Melioidosis
AU - Weehuizen, Tassili A. F.
AU - Wieland, Catharina W.
AU - van der Windt, Gerritje J. W.
AU - Duitman, Jan-Willem
AU - Boon, Louis
AU - Day, Nicholas P. J.
AU - Peacock, Sharon J.
AU - van der Poll, Tom
AU - Wiersinga, W. Joost
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
U2 - https://doi.org/10.1128/IAI.05534-11
DO - https://doi.org/10.1128/IAI.05534-11
M3 - Article
C2 - 22331429
SN - 0019-9567
VL - 80
SP - 1853
EP - 1857
JO - Infection and immunity
JF - Infection and immunity
IS - 5
ER -