| Development of new antituberculous drugs based on bacterial virulence factors interfering with host cytokine networks. | |
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MedLine Citation:
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PMID: 21243398 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The worldwide increase in the prevalence of tuberculosis (TB), especially multidrug-resistant TB and extensively drug-resistant TB, is an important global health concern, and new effective drugs are urgently needed. Information on the genome of Mycobacterium tuberculosis (MTB) and various mycobacterial virulence genes is leading to the identification of genes that code for new drug targets. Mycobacterium tuberculosis (MTB) is resistant to the antimicrobial mechanisms of host macrophages and can survive and replicate in macrophages for long periods, resulting in a persistent infection. Mycobacterial virulence factors suppress macrophage bactericidal functions partly via their downregulatory effects on the host antimicrobial cytokine networks, consisting of proinflammatory, immunopotentiating, and Th1-inducing cytokines. Thus, for the development of unique drugs that exhibit antimycobacterial action through novel mechanisms, it is reasonable to search for targets among bacterial genes encoding virulence factors which interfere with the host cytokine responses protective to mycobacterial pathogens. In this review, we discuss the profiles of cytokine networks related to host resistance to mycobacteria, including the mechanisms of downregulation of host antimycobacterial immunity due to immunosuppressive cytokines, which are occasionally induced in the advanced stages of TB. We also highlight the development of antituberculous drugs based on bacterial virulence factors interfering with the host antimycobacterial cytokine network. |
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Authors:
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Haruaki Tomioka; Yutaka Tatano; Chiaki Sano; Toshiaki Shimizu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-18 |
Journal Detail:
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Title: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Volume: - ISSN: 1437-7780 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9608375 Medline TA: J Infect Chemother Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Microbiology and Immunology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan, tomioka@med.shimane-u.ac.jp. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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