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Antimicrobial Agents and Chemotherapy, May 2006, p. 1798-1804, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1798-1804.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Minocycline Impedes African Trypanosome Invasion of the Brain in a Murine Model

Willias Masocha,1* Martin E. Rottenberg,2 and Krister Kristensson1

Department of Neuroscience,1 Microbiology and Tumor Biology Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden2

Received 12 October 2005/ Returned for modification 28 November 2005/ Accepted 17 February 2006

Passage of Trypanosoma brucei across the blood-brain barrier (BBB) is a hallmark of late-stage human African trypanosomiasis. In the present study we found that daily administration of minocycline, a tetracycline antibiotic, impedes the penetration of leukocytes and trypanosomes into the brain parenchyma of T. brucei brucei-infected C57BL/6 mice. The trypanosome-induced astrocytic and microglial reactions were reduced in the minocycline-treated mice, as were the levels in the brain of transcripts encoding adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and endothelial-leukocyte adhesion molecule 1 (E-selectin); the inflammatory cytokines tumor necrosis factor alpha, interleukin-1{alpha} (IL-1{alpha}), IL-1ß, IL-6, and gamma interferon; and matrix metalloprotease 3 (MMP-3), MMP-8, and MMP-12. Loss of weight occurring during infection with T. b. brucei was not observed after treatment of the mice with minocycline; these mice also survived longer than nontreated mice. Invasion of trypanosomes and leukocytes into the brain parenchyma most likely triggered the loss of weight and death of infected animals, since minocycline did not affect the growth of T. b. brucei either in vitro or in vivo or the levels of the transcripts encoding the cytokines and MMPs in the spleen. In conclusion, our data show that T. b. brucei invasion of the brain is related to that of leukocytes and that minocycline can ameliorate the disease in trypanosome-infected mice.

* Corresponding author. Mailing address: Department of Neuroscience, Retzius väg 8, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Phone: 46-8-524-878-10. Fax: 46-8-32-53-25. E-mail: willias.masocha{at}ki.se.

Antimicrobial Agents and Chemotherapy, May 2006, p. 1798-1804, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1798-1804.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Antoine-Moussiaux, N., Buscher, P., Desmecht, D. (2009). Host-Parasite Interactions in Trypanosomiasis: on the Way to an Antidisease Strategy. Infect. Immun. 77: 1276-1284 [Full Text]  
  • Kielian, T., Esen, N., Liu, S., Phulwani, N. K., Syed, M. M., Phillips, N., Nishina, K., Cheung, A. L., Schwartzman, J. D., Ruhe, J. J. (2007). Minocycline Modulates Neuroinflammation Independently of Its Antimicrobial Activity in Staphylococcus aureus-Induced Brain Abscess. Am. J. Pathol. 171: 1199-1214 [Abstract] [Full Text]  


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