Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response
Inhibition of apoptosis of infected macrophages by pathogenic mycobacteria is suggested to be an important virulence mechanism, but little is known about the mycobacterial proteins involved in the inhibition of apoptosis. In this study we investigated differences in apoptosis and immune response and...
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| description | Inhibition of apoptosis of infected macrophages by pathogenic mycobacteria is suggested to be an important virulence mechanism, but little is known about the mycobacterial proteins involved in the inhibition of apoptosis. In this study we investigated differences in apoptosis and immune response and their correlation with the expression of Mycobacterium tuberculosis complex-specific secretory protein MPT64 in lesions caused by tuberculous or non-tuberculous mycobacteria by analysing the in situ expression of apoptosis-related proteins (FasL, Fas, Bax, Bcl-2), apoptotic cells, inflammatory cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-10, transforming growth factor (TGF)-β, interferon (IFN)-γ] and MPT64 antigen. The discrimination of mycobacteria was made by nested polymerase chain reaction (PCR) amplification of IS6110, which is specific for M. tuberculosis complex organisms. Forty-seven cases of lymphadenitis with necrotic granulomas were evaluated. With nested PCR, 30/47 cases were positive for M. tuberculosis. MPT64 antigen was detected specifically in the PCR-positive cases. Granulomas caused by tuberculous mycobacteria had fewer apoptotic cells, higher numbers of cells expressing TNF-α and TGF-β and less extensive necrosis than granulomas caused by non-tuberculous mycobacteria. There was a significant negative correlation between apoptotic cells and the number of cells expressing MPT64 antigens, suggesting a role for MPT64 protein in the inhibition of apoptosis. Granulomas with higher amounts of MPT64 also showed a greater number of cells expressing TGF-β than those with lower amounts of MPT64. In conclusion, this study supports the hypothesis that inhibition of apoptosis is a virulence mechanism for tuberculous mycobacteria. Correlation of MPT64 antigen with expression of macrophage deactivating cytokines and reduced apoptosis suggests its role in pathogenesis and bacillary persistence. |
| doi_str_mv | 10.1111/j.1365-2249.2007.03476.x |
| format | Article |
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In this study we investigated differences in apoptosis and immune response and their correlation with the expression of Mycobacterium tuberculosis complex-specific secretory protein MPT64 in lesions caused by tuberculous or non-tuberculous mycobacteria by analysing the in situ expression of apoptosis-related proteins (FasL, Fas, Bax, Bcl-2), apoptotic cells, inflammatory cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-10, transforming growth factor (TGF)-β, interferon (IFN)-γ] and MPT64 antigen. The discrimination of mycobacteria was made by nested polymerase chain reaction (PCR) amplification of IS6110, which is specific for M. tuberculosis complex organisms. Forty-seven cases of lymphadenitis with necrotic granulomas were evaluated. With nested PCR, 30/47 cases were positive for M. tuberculosis. MPT64 antigen was detected specifically in the PCR-positive cases. Granulomas caused by tuberculous mycobacteria had fewer apoptotic cells, higher numbers of cells expressing TNF-α and TGF-β and less extensive necrosis than granulomas caused by non-tuberculous mycobacteria. There was a significant negative correlation between apoptotic cells and the number of cells expressing MPT64 antigens, suggesting a role for MPT64 protein in the inhibition of apoptosis. Granulomas with higher amounts of MPT64 also showed a greater number of cells expressing TGF-β than those with lower amounts of MPT64. In conclusion, this study supports the hypothesis that inhibition of apoptosis is a virulence mechanism for tuberculous mycobacteria. Correlation of MPT64 antigen with expression of macrophage deactivating cytokines and reduced apoptosis suggests its role in pathogenesis and bacillary persistence.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/j.1365-2249.2007.03476.x</identifier><identifier>PMID: 17711491</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford, UK: Oxford, UK : Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analytical, structural and metabolic biochemistry ; Antigens, Bacterial - immunology ; Antigens, Bacterial - metabolism ; Apoptosis ; Bacterial Proteins - immunology ; Bacterial Proteins - metabolism ; bcl-2-Associated X Protein - metabolism ; Biological and medical sciences ; Child ; Child, Preschool ; cytokines ; Cytokines - metabolism ; Fas Ligand Protein - metabolism ; fas Receptor - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Granuloma - immunology ; Granuloma - microbiology ; Granuloma - pathology ; granulomas ; Humans ; Inflammation Mediators - metabolism ; Lymph Nodes - immunology ; Lymph Nodes - pathology ; Male ; Middle Aged ; Molecular and cellular biology ; Molecular biophysics ; MPT64 ; Mycobacterium - immunology ; Mycobacterium Infections - immunology ; Mycobacterium Infections - pathology ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Mycobacterium tuberculosis - pathogenicity ; Polymerase Chain Reaction - methods ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Translational Studies ; Tuberculosis, Lymph Node - immunology ; Tuberculosis, Lymph Node - microbiology ; Tuberculosis, Lymph Node - pathology ; tuberculous mycobacteria ; Virulence</subject><ispartof>Clinical and experimental immunology, 2007-10, Vol.150 (1), p.105-113</ispartof><rights>2008 INIST-CNRS</rights><rights>2007 British Society for Immunology 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5576-7cbe499e5d8de1bea118c1bfef37055b428bdf9154c5a5455ded7ec026d2c2de3</citedby><cites>FETCH-LOGICAL-c5576-7cbe499e5d8de1bea118c1bfef37055b428bdf9154c5a5455ded7ec026d2c2de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219281/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219281/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19071014$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17711491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mustafa, T</creatorcontrib><creatorcontrib>Wiker, H.G</creatorcontrib><creatorcontrib>Mørkve, O</creatorcontrib><creatorcontrib>Sviland, L</creatorcontrib><title>Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Inhibition of apoptosis of infected macrophages by pathogenic mycobacteria is suggested to be an important virulence mechanism, but little is known about the mycobacterial proteins involved in the inhibition of apoptosis. In this study we investigated differences in apoptosis and immune response and their correlation with the expression of Mycobacterium tuberculosis complex-specific secretory protein MPT64 in lesions caused by tuberculous or non-tuberculous mycobacteria by analysing the in situ expression of apoptosis-related proteins (FasL, Fas, Bax, Bcl-2), apoptotic cells, inflammatory cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-10, transforming growth factor (TGF)-β, interferon (IFN)-γ] and MPT64 antigen. The discrimination of mycobacteria was made by nested polymerase chain reaction (PCR) amplification of IS6110, which is specific for M. tuberculosis complex organisms. Forty-seven cases of lymphadenitis with necrotic granulomas were evaluated. With nested PCR, 30/47 cases were positive for M. tuberculosis. MPT64 antigen was detected specifically in the PCR-positive cases. Granulomas caused by tuberculous mycobacteria had fewer apoptotic cells, higher numbers of cells expressing TNF-α and TGF-β and less extensive necrosis than granulomas caused by non-tuberculous mycobacteria. There was a significant negative correlation between apoptotic cells and the number of cells expressing MPT64 antigens, suggesting a role for MPT64 protein in the inhibition of apoptosis. Granulomas with higher amounts of MPT64 also showed a greater number of cells expressing TGF-β than those with lower amounts of MPT64. In conclusion, this study supports the hypothesis that inhibition of apoptosis is a virulence mechanism for tuberculous mycobacteria. Correlation of MPT64 antigen with expression of macrophage deactivating cytokines and reduced apoptosis suggests its role in pathogenesis and bacillary persistence.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Antigens, Bacterial - immunology</subject><subject>Antigens, Bacterial - metabolism</subject><subject>Apoptosis</subject><subject>Bacterial Proteins - immunology</subject><subject>Bacterial Proteins - metabolism</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>cytokines</subject><subject>Cytokines - metabolism</subject><subject>Fas Ligand Protein - metabolism</subject><subject>fas Receptor - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Granuloma - immunology</subject><subject>Granuloma - microbiology</subject><subject>Granuloma - pathology</subject><subject>granulomas</subject><subject>Humans</subject><subject>Inflammation Mediators - metabolism</subject><subject>Lymph Nodes - immunology</subject><subject>Lymph Nodes - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Molecular biophysics</subject><subject>MPT64</subject><subject>Mycobacterium - immunology</subject><subject>Mycobacterium Infections - immunology</subject><subject>Mycobacterium Infections - pathology</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Mycobacterium tuberculosis - pathogenicity</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Translational Studies</subject><subject>Tuberculosis, Lymph Node - immunology</subject><subject>Tuberculosis, Lymph Node - microbiology</subject><subject>Tuberculosis, Lymph Node - pathology</subject><subject>tuberculous mycobacteria</subject><subject>Virulence</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1DAQxyMEotvCK4AvcMtiO3E-kEBCqxYqFYGgPVsTe7J4SexgJ9A8Gy-Hw67awgV88XjmNx-2_0lCGF2zuF7s1iwrRMp5Xq85peWaZnlZrK_vJaubwP1kRSmt05rR_Cg5DmEXj0VR8IfJEStLxvKarZKfn1BPCjWBwQ2jCyYQsJoYqzxCwMVqO-h7GJ2fiZpH99VYDNFNth7s1LkeAlEwLWwzk3Fq0KvonqLX9QP46B8dsc6md2P9rFwDakRv4CXxrkPiWvL-42WRxwFGs0W79Phrqr6fLBKPYXA24KPkQQtdwMeH_SS5Oju93LxLLz68Pd-8uUiVEGWRlqrBvK5R6EojaxAYqxRrWmyzkgrR5LxqdFszkSsBIhdCoy5RUV5orrjG7CR5va87TE2PWqEdPXRy8KYHP0sHRv4ZseaL3LrvknNW84rFAs8PBbz7NmEYZW-Cwq4Di_ExZFFxUQlR_xPkVNCCsyyC1R5U3oXgsb2ZhlG5SETu5KIEuShBLhKRvyUir2Pqk7u3uU08aCICzw4ABAVdG79ZmXDL1bRklOWRe7XnfpgO5_8eQG5Ozxcr5j_d57fgJGx97HH1mVOWUVpRXpV59gvfc-e9</recordid><startdate>200710</startdate><enddate>200710</enddate><creator>Mustafa, T</creator><creator>Wiker, H.G</creator><creator>Mørkve, O</creator><creator>Sviland, L</creator><general>Oxford, UK : Blackwell Publishing Ltd</general><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Blackwell Science Inc</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200710</creationdate><title>Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response</title><author>Mustafa, T ; Wiker, H.G ; Mørkve, O ; Sviland, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5576-7cbe499e5d8de1bea118c1bfef37055b428bdf9154c5a5455ded7ec026d2c2de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Antigens, Bacterial - immunology</topic><topic>Antigens, Bacterial - metabolism</topic><topic>Apoptosis</topic><topic>Bacterial Proteins - immunology</topic><topic>Bacterial Proteins - metabolism</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>cytokines</topic><topic>Cytokines - metabolism</topic><topic>Fas Ligand Protein - metabolism</topic><topic>fas Receptor - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Granuloma - immunology</topic><topic>Granuloma - microbiology</topic><topic>Granuloma - pathology</topic><topic>granulomas</topic><topic>Humans</topic><topic>Inflammation Mediators - metabolism</topic><topic>Lymph Nodes - immunology</topic><topic>Lymph Nodes - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular and cellular biology</topic><topic>Molecular biophysics</topic><topic>MPT64</topic><topic>Mycobacterium - immunology</topic><topic>Mycobacterium Infections - immunology</topic><topic>Mycobacterium Infections - pathology</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Mycobacterium tuberculosis - pathogenicity</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Translational Studies</topic><topic>Tuberculosis, Lymph Node - immunology</topic><topic>Tuberculosis, Lymph Node - microbiology</topic><topic>Tuberculosis, Lymph Node - pathology</topic><topic>tuberculous mycobacteria</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mustafa, T</creatorcontrib><creatorcontrib>Wiker, H.G</creatorcontrib><creatorcontrib>Mørkve, O</creatorcontrib><creatorcontrib>Sviland, L</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mustafa, T</au><au>Wiker, H.G</au><au>Mørkve, O</au><au>Sviland, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2007-10</date><risdate>2007</risdate><volume>150</volume><issue>1</issue><spage>105</spage><epage>113</epage><pages>105-113</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>Inhibition of apoptosis of infected macrophages by pathogenic mycobacteria is suggested to be an important virulence mechanism, but little is known about the mycobacterial proteins involved in the inhibition of apoptosis. In this study we investigated differences in apoptosis and immune response and their correlation with the expression of Mycobacterium tuberculosis complex-specific secretory protein MPT64 in lesions caused by tuberculous or non-tuberculous mycobacteria by analysing the in situ expression of apoptosis-related proteins (FasL, Fas, Bax, Bcl-2), apoptotic cells, inflammatory cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-10, transforming growth factor (TGF)-β, interferon (IFN)-γ] and MPT64 antigen. The discrimination of mycobacteria was made by nested polymerase chain reaction (PCR) amplification of IS6110, which is specific for M. tuberculosis complex organisms. Forty-seven cases of lymphadenitis with necrotic granulomas were evaluated. With nested PCR, 30/47 cases were positive for M. tuberculosis. MPT64 antigen was detected specifically in the PCR-positive cases. Granulomas caused by tuberculous mycobacteria had fewer apoptotic cells, higher numbers of cells expressing TNF-α and TGF-β and less extensive necrosis than granulomas caused by non-tuberculous mycobacteria. There was a significant negative correlation between apoptotic cells and the number of cells expressing MPT64 antigens, suggesting a role for MPT64 protein in the inhibition of apoptosis. Granulomas with higher amounts of MPT64 also showed a greater number of cells expressing TGF-β than those with lower amounts of MPT64. In conclusion, this study supports the hypothesis that inhibition of apoptosis is a virulence mechanism for tuberculous mycobacteria. Correlation of MPT64 antigen with expression of macrophage deactivating cytokines and reduced apoptosis suggests its role in pathogenesis and bacillary persistence.</abstract><cop>Oxford, UK</cop><pub>Oxford, UK : Blackwell Publishing Ltd</pub><pmid>17711491</pmid><doi>10.1111/j.1365-2249.2007.03476.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Analytical, structural and metabolic biochemistry Antigens, Bacterial - immunology Antigens, Bacterial - metabolism Apoptosis Bacterial Proteins - immunology Bacterial Proteins - metabolism bcl-2-Associated X Protein - metabolism Biological and medical sciences Child Child, Preschool cytokines Cytokines - metabolism Fas Ligand Protein - metabolism fas Receptor - metabolism Female Fundamental and applied biological sciences. Psychology Granuloma - immunology Granuloma - microbiology Granuloma - pathology granulomas Humans Inflammation Mediators - metabolism Lymph Nodes - immunology Lymph Nodes - pathology Male Middle Aged Molecular and cellular biology Molecular biophysics MPT64 Mycobacterium - immunology Mycobacterium Infections - immunology Mycobacterium Infections - pathology Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Mycobacterium tuberculosis - pathogenicity Polymerase Chain Reaction - methods Proto-Oncogene Proteins c-bcl-2 - metabolism Translational Studies Tuberculosis, Lymph Node - immunology Tuberculosis, Lymph Node - microbiology Tuberculosis, Lymph Node - pathology tuberculous mycobacteria Virulence |
| title | Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response |
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