A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection
IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tub...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2001-12, Vol.167 (12), p.6957-6966 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6966 |
|---|---|
| container_issue | 12 |
| container_start_page | 6957 |
| container_title | The Journal of immunology (1950) |
| container_volume | 167 |
| creator | Holscher, Christoph Atkinson, Robert A Arendse, Berenice Brown, Najmeeyah Myburgh, Elmarie Alber, Gottfried Brombacher, Frank |
| description | IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70. |
| doi_str_mv | 10.4049/jimmunol.167.12.6957 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72343169</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>18145307</sourcerecordid><originalsourceid>FETCH-LOGICAL-c479t-15e6a6944c6a959219477d0bd57ed71b876572207550024f0dd68ba6c6f5b7d73</originalsourceid><addsrcrecordid>eNqFkMtOwzAQRS0EouXxBwh5hdikeBw_6mWFKBQVwQLWluM44CqJS5wQ8fektAh2rEYanXs1cxA6AzJhhKmrla-qrg7lBIScAJ0IxeUeGgPnJBGCiH00JoTSBKSQI3QU44oQIghlh2gEIFPFgY_R_Qw_NaF1tvUfDps6x7PXUPvYeovnXT2sQ41DgRfLBOiaEexr_PBpQ2Zs6xpvSryoC_eNnaCDwpTRne7mMXqZ3zxf3yXLx9vF9WyZWCZVmwB3wgjFmBVGcUVBMSlzkuVculxCNpWCS0qJHB4Zri1InotpZoQVBc9kLtNjdLHtXTfhvXOx1ZWP1pWlqV3oopY0ZSkI9S8IU2A8JZtGtgVtE2JsXKHXja9M86mB6I1s_SNbD7I1UL2RPcTOd_1dVrn8N7SzOwCXW-DNv771vnE6VqYsBxx03_d_u74AheiIfw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18145307</pqid></control><display><type>article</type><title>A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Holscher, Christoph ; Atkinson, Robert A ; Arendse, Berenice ; Brown, Najmeeyah ; Myburgh, Elmarie ; Alber, Gottfried ; Brombacher, Frank</creator><creatorcontrib>Holscher, Christoph ; Atkinson, Robert A ; Arendse, Berenice ; Brown, Najmeeyah ; Myburgh, Elmarie ; Alber, Gottfried ; Brombacher, Frank</creatorcontrib><description>IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.167.12.6957</identifier><identifier>PMID: 11739515</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; Antigens, Bacterial - immunology ; Cells, Cultured ; Colony Count, Microbial ; Granuloma - immunology ; Granuloma - microbiology ; Granuloma - pathology ; Hypersensitivity, Delayed - immunology ; Interleukin-12 - genetics ; Interleukin-12 - pharmacology ; Interleukin-12 - physiology ; Interleukin-23 ; Interleukin-23 Subunit p19 ; Interleukins - biosynthesis ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mycobacterium bovis ; Mycobacterium bovis - growth & development ; Mycobacterium bovis - immunology ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - growth & development ; Mycobacterium tuberculosis - immunology ; p35 protein ; p40 protein ; Protein Subunits ; Survival Rate ; T-Lymphocytes, Cytotoxic - immunology ; Th1 Cells - immunology ; Tuberculosis, Pulmonary - drug therapy ; Tuberculosis, Pulmonary - immunology ; Tuberculosis, Pulmonary - pathology</subject><ispartof>The Journal of immunology (1950), 2001-12, Vol.167 (12), p.6957-6966</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-15e6a6944c6a959219477d0bd57ed71b876572207550024f0dd68ba6c6f5b7d73</citedby><cites>FETCH-LOGICAL-c479t-15e6a6944c6a959219477d0bd57ed71b876572207550024f0dd68ba6c6f5b7d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11739515$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holscher, Christoph</creatorcontrib><creatorcontrib>Atkinson, Robert A</creatorcontrib><creatorcontrib>Arendse, Berenice</creatorcontrib><creatorcontrib>Brown, Najmeeyah</creatorcontrib><creatorcontrib>Myburgh, Elmarie</creatorcontrib><creatorcontrib>Alber, Gottfried</creatorcontrib><creatorcontrib>Brombacher, Frank</creatorcontrib><title>A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70.</description><subject>Animals</subject><subject>Antigens, Bacterial - immunology</subject><subject>Cells, Cultured</subject><subject>Colony Count, Microbial</subject><subject>Granuloma - immunology</subject><subject>Granuloma - microbiology</subject><subject>Granuloma - pathology</subject><subject>Hypersensitivity, Delayed - immunology</subject><subject>Interleukin-12 - genetics</subject><subject>Interleukin-12 - pharmacology</subject><subject>Interleukin-12 - physiology</subject><subject>Interleukin-23</subject><subject>Interleukin-23 Subunit p19</subject><subject>Interleukins - biosynthesis</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mycobacterium bovis</subject><subject>Mycobacterium bovis - growth & development</subject><subject>Mycobacterium bovis - immunology</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - growth & development</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>p35 protein</subject><subject>p40 protein</subject><subject>Protein Subunits</subject><subject>Survival Rate</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Th1 Cells - immunology</subject><subject>Tuberculosis, Pulmonary - drug therapy</subject><subject>Tuberculosis, Pulmonary - immunology</subject><subject>Tuberculosis, Pulmonary - pathology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAQRS0EouXxBwh5hdikeBw_6mWFKBQVwQLWluM44CqJS5wQ8fektAh2rEYanXs1cxA6AzJhhKmrla-qrg7lBIScAJ0IxeUeGgPnJBGCiH00JoTSBKSQI3QU44oQIghlh2gEIFPFgY_R_Qw_NaF1tvUfDps6x7PXUPvYeovnXT2sQ41DgRfLBOiaEexr_PBpQ2Zs6xpvSryoC_eNnaCDwpTRne7mMXqZ3zxf3yXLx9vF9WyZWCZVmwB3wgjFmBVGcUVBMSlzkuVculxCNpWCS0qJHB4Zri1InotpZoQVBc9kLtNjdLHtXTfhvXOx1ZWP1pWlqV3oopY0ZSkI9S8IU2A8JZtGtgVtE2JsXKHXja9M86mB6I1s_SNbD7I1UL2RPcTOd_1dVrn8N7SzOwCXW-DNv771vnE6VqYsBxx03_d_u74AheiIfw</recordid><startdate>20011215</startdate><enddate>20011215</enddate><creator>Holscher, Christoph</creator><creator>Atkinson, Robert A</creator><creator>Arendse, Berenice</creator><creator>Brown, Najmeeyah</creator><creator>Myburgh, Elmarie</creator><creator>Alber, Gottfried</creator><creator>Brombacher, Frank</creator><general>Am Assoc Immnol</general><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></search><sort><creationdate>20011215</creationdate><title>A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection</title><author>Holscher, Christoph ; Atkinson, Robert A ; Arendse, Berenice ; Brown, Najmeeyah ; Myburgh, Elmarie ; Alber, Gottfried ; Brombacher, Frank</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-15e6a6944c6a959219477d0bd57ed71b876572207550024f0dd68ba6c6f5b7d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Antigens, Bacterial - immunology</topic><topic>Cells, Cultured</topic><topic>Colony Count, Microbial</topic><topic>Granuloma - immunology</topic><topic>Granuloma - microbiology</topic><topic>Granuloma - pathology</topic><topic>Hypersensitivity, Delayed - immunology</topic><topic>Interleukin-12 - genetics</topic><topic>Interleukin-12 - pharmacology</topic><topic>Interleukin-12 - physiology</topic><topic>Interleukin-23</topic><topic>Interleukin-23 Subunit p19</topic><topic>Interleukins - biosynthesis</topic><topic>Lymphocyte Activation</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mycobacterium bovis</topic><topic>Mycobacterium bovis - growth & development</topic><topic>Mycobacterium bovis - immunology</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - growth & development</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>p35 protein</topic><topic>p40 protein</topic><topic>Protein Subunits</topic><topic>Survival Rate</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Th1 Cells - immunology</topic><topic>Tuberculosis, Pulmonary - drug therapy</topic><topic>Tuberculosis, Pulmonary - immunology</topic><topic>Tuberculosis, Pulmonary - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Holscher, Christoph</creatorcontrib><creatorcontrib>Atkinson, Robert A</creatorcontrib><creatorcontrib>Arendse, Berenice</creatorcontrib><creatorcontrib>Brown, Najmeeyah</creatorcontrib><creatorcontrib>Myburgh, Elmarie</creatorcontrib><creatorcontrib>Alber, Gottfried</creatorcontrib><creatorcontrib>Brombacher, Frank</creatorcontrib><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><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holscher, Christoph</au><au>Atkinson, Robert A</au><au>Arendse, Berenice</au><au>Brown, Najmeeyah</au><au>Myburgh, Elmarie</au><au>Alber, Gottfried</au><au>Brombacher, Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2001-12-15</date><risdate>2001</risdate><volume>167</volume><issue>12</issue><spage>6957</spage><epage>6966</epage><pages>6957-6966</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11739515</pmid><doi>10.4049/jimmunol.167.12.6957</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2001-12, Vol.167 (12), p.6957-6966 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72343169 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antigens, Bacterial - immunology Cells, Cultured Colony Count, Microbial Granuloma - immunology Granuloma - microbiology Granuloma - pathology Hypersensitivity, Delayed - immunology Interleukin-12 - genetics Interleukin-12 - pharmacology Interleukin-12 - physiology Interleukin-23 Interleukin-23 Subunit p19 Interleukins - biosynthesis Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Mycobacterium bovis Mycobacterium bovis - growth & development Mycobacterium bovis - immunology Mycobacterium tuberculosis Mycobacterium tuberculosis - growth & development Mycobacterium tuberculosis - immunology p35 protein p40 protein Protein Subunits Survival Rate T-Lymphocytes, Cytotoxic - immunology Th1 Cells - immunology Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - pathology |
| title | A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T22%3A37%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Protective%20and%20Agonistic%20Function%20of%20IL-12p40%20in%20Mycobacterial%20Infection&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Holscher,%20Christoph&rft.date=2001-12-15&rft.volume=167&rft.issue=12&rft.spage=6957&rft.epage=6966&rft.pages=6957-6966&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.167.12.6957&rft_dat=%3Cproquest_cross%3E18145307%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18145307&rft_id=info:pmid/11739515&rfr_iscdi=true |