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Microb Pathog. 2005 Nov-Dec;39(5-6):189-96. Epub 2005 Oct 28.

Low dose aerosol infection of mice with virulent type A Francisella tularensis induces severe thymus atrophy and CD4+CD8+ thymocyte depletion.

Author information

1
Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ont., Canada K1A 0R6. wangxue.chen@nrc.gc.ca

Abstract

Francisella tularensis is a gram-negative facultative intracellular bacterium and the causative agent of tularemia. Two subspecies (type A and B strains) of the pathogen exist, the former being much more virulent than the latter for humans and other higher mammals. In this study, we examined the effect of virulent strains of F. tularensis infection on the thymus and thymocytes and the potential mechanisms involved. Low-dose aerosol exposure of C57BL/6 mice with type A, but not type B, F. tularensis caused severe reduction in thymus weight and destruction of thymocytes, particularly CD4+CD8+ thymocytes, by day 4 after infection. The depletion of thymocytes was accompanied by a significant increase in circulating cortisone levels and could be partially prevented by adrenalectomy. Moreover, thymus atrophy and thymocyte depletion following infection were abolished in mice deficient in tumor necrosis factor receptors 1 and 2, but not in FasL-deficient mice. The severe destruction of the thymus and selective depletion of immature thymocytes during type A F. tularensis infection may represent a key pathogenic mechanism in tularemia and could hinder the development of an effective primary immune response against this highly virulent pathogen.

PMID:
16257504
PMCID:
PMC1564440
DOI:
10.1016/j.micpath.2005.08.005
[Indexed for MEDLINE]
Free PMC Article

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