HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Stewart, J. N. Articles by Rivera-Marrero, C. A. Search for Related Content PubMed PubMed Citation Articles by Stewart, J. N. Articles by Rivera-Marrero, C. A. Agricola Articles by Stewart, J. N. Articles by Rivera-Marrero, C. A.

Increased pathology in lungs of mice after infection with an -crystallin mutant of Mycobacterium tuberculosis: changes in cathepsin proteases and certain cytokines

¹ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Athens, GA 30602, USA
² Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
³ Atlanta VA Medical Center Research Service, Room 12C 106, 1670 Clairmont Rd, Decatur, GA 30033, USA

Correspondence
Carlos A. Rivera-Marrero
crivera{at}emory.edu

Latency and reactivation are a significant problem that contributes to the incidence, transmission and pathogenesis of tuberculosis. The mechanisms involved in these processes, at the level of both the bacillus and the host, are poorly understood. In Mycobacterium tuberculosis the -crystallin (acr) gene has been linked to latency, because it is highly expressed during hypoxic growth conditions. Deletion of the acr gene in M. tuberculosis H37Rv (acr strain) was previously shown to reduce the intracellular growth of bacilli in macrophages; however, its impact on pathogenesis in vivo was unknown. This study demonstrated that infection of C57BL6 mice with acr results in lung bacillary loads 1-2 log units higher in comparison to parental H37Rv. Haematoxylin/eosin staining of lungs revealed exacerbated pathology characterized by extensive obliteration of alveolar air spaces by granulomatous inflammation. RT-PCR analysis and immunostaining of lungs showed that infection with either H37Rv or acr results in the differential expression of lysosomal cathepsin proteases. A slight increase in the expression of the matrix-degrading acidic-type cathepsins B, D and H was noted in acr-infected mice and was associated with clusters of macrophages within lung granulomas. acr-infected mice also showed high serum levels of TNF-, IFN- and G-CSF, suggesting that Acr may play a role in modulating the host response to infection.

This article has been cited by other articles:

				H. M. Vasudeva-Rao and K. A. McDonough Expression of the Mycobacterium tuberculosis acr-Coregulated Genes from the DevR (DosR) Regulon Is Controlled by Multiple Levels of Regulation Infect. Immun., June 1, 2008; 76(6): 2478 - 2489. [Abstract] [Full Text] [PDF]