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Infection and Immunity, April 2002, p. 2121-2127, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2121-2127.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Upregulation of Thymosin ß-10 by Mycobacterium bovis Infection of Bovine Macrophages Is Associated with Apoptosis

José A. Gutiérrez-Pabello,1,{dagger} David N. McMurray,2 and L. Garry Adams1*

Department of Veterinary Pathobiology, College of Veterinary Medicine,1 Department of Medical Microbiology, College of Medicine, Texas A&M University, College Station, Texas 778432

Received 24 August 2001/ Returned for modification 1 November 2001/ Accepted 10 January 2002

Bovine macrophages underwent apoptosis as a result of infection with a Mycobacterium bovis field strain. Macrophages infected with a multiplicity of infection (MOI) of 25:1 developed chromatin condensation and DNA fragmentation at 4 h and 8 h, respectively, whereas changes in chromatin condensation induced by MOIs of 10:1 and 1:1 required more time and had a reduced number of apoptotic cells. Not only infected macrophages underwent apoptosis, but also uninfected bystander macrophages became apoptotic. Increased differential expression of thymosin ß-10 was identified in M. bovis-infected bovine macrophages by differential display reverse transcriptase PCR. Phagocytosis of latex beads had no effect on the expression of thymosin ß-10, whereas bacterial suspensions upregulated thymosin ß-10 expression, suggesting that M. bovis or mycobacterial products are essential in the process. Heat-inactivated M. bovis induced a slight increase in thymosin ß-10 mRNA, whereas live virulent and attenuated M. bovis organisms increased the gene expression almost twofold. A mouse macrophage cell line (RAW 264.7) overexpressing the bovine thymosin ß-10 transgene had spontaneous apoptosis at a higher rate (66.5%) than parental cells (4.7%) or RAW cells harboring the empty vector (22.8%). The apoptotic rates of the overexpressing cells were significantly higher when compared with both the empty vector transfected (P < 0.01) and parental cells (P < 0.001). Our evidence suggests that upregulation of thymosin ß-10 in M. bovis-infected macrophages is linked with increased cell death due to apoptosis.

* Corresponding author. Mailing address: Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4467. Phone: (979) 845-5092. Fax: (979) 845-5088. E-mail: gadams{at}cvm.tamu.edu.

Editor: R. N. Moore

{dagger} Present address: Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autonoma de México, México City, Mexico 04510.

Infection and Immunity, April 2002, p. 2121-2127, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2121-2127.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vega-Manriquez, X., Lopez-Vidal, Y., Moran, J., Adams, L. G., Gutierrez-Pabello, J. A. (2007). Apoptosis-Inducing Factor Participation in Bovine Macrophage Mycobacterium bovis-Induced Caspase-Independent Cell Death. Infect. Immun. 75: 1223-1228 [Abstract] [Full Text]  
  • Rho, S. B., Lee, K. W., Chun, T., Lee, S.-H., Park, K., Lee, J.-H. (2005). The Identification of Apoptosis-related Residues in Human Thymosin {beta}-10 by Mutational Analysis and Computational Modeling. J. Biol. Chem. 280: 34003-34007 [Abstract] [Full Text]  


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