Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression
Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory funct...
Gespeichert in:
| Veröffentlicht in: | The Journal of infectious diseases 2011-03, Vol.203 (5), p.715-725 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 725 |
|---|---|
| container_issue | 5 |
| container_start_page | 715 |
| container_title | The Journal of infectious diseases |
| container_volume | 203 |
| creator | Makala, Levi H. C. Baban, Babak Lemos, Henrique El-Awady, Ahmed R. Chandler, Phillip R. Hou, De-Yan Munn, David H. Mellor, Andrew L. |
| description | Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4⁺ T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections. |
| doi_str_mv | 10.1093/infdis/jiq095 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3072725</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>25801800</jstor_id><oup_id>10.1093/infdis/jiq095</oup_id><sourcerecordid>25801800</sourcerecordid><originalsourceid>FETCH-LOGICAL-c570t-faf978d8039363469c5449ae95aee9c375b5eff471f211095654274a9baac0f23</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhiMEoqVw5AjyBakHQv0Rx_EFqWoLXWklDsDZmvWOt14l9tZ2UPffE5RlW06cZqR55p2Pt6reMvqJUS0ufHBrny-2_p5q-aw6pZTzmnVaP3-Sn1Svct5SShvRqpfVCWe840y3pxUu0ee7AYIHMsA2JnJZCoYRCmZyG3Mhi2EYgy97stqT78UPYw_Fhw1ZRgs9WYR17BEGH5Dwj6K-9vFhv8EAGcnNwy5hzj6G19ULB33GN4d4Vv38cvPj6rZefvu6uLpc1lYqWmoHTqtu3VGhRSuaVlvZNBpQS0DUVii5kuhco5jjbLpetrLhqgG9ArDUcXFWfZ51d-NqwLXFUBL0Zpf8AGlvInjzbyX4O7OJv4ygiisuJ4Hzg0CK9yPmYgafLfY9BIxjNqwVWmsuVTeh9YzaFHNO6I5jGDV_rDGzNWa2ZuLfP93tSP_1YgI-HADI02tdgmCn9iMndMtkox53jOPuvzPfzeg2l5gepWRHWUep-A2KkLJ2</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1639992578</pqid></control><display><type>article</type><title>Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>JSTOR All Journals</source><source>Alma/SFX Local Collection</source><creator>Makala, Levi H. C. ; Baban, Babak ; Lemos, Henrique ; El-Awady, Ahmed R. ; Chandler, Phillip R. ; Hou, De-Yan ; Munn, David H. ; Mellor, Andrew L.</creator><creatorcontrib>Makala, Levi H. C. ; Baban, Babak ; Lemos, Henrique ; El-Awady, Ahmed R. ; Chandler, Phillip R. ; Hou, De-Yan ; Munn, David H. ; Mellor, Andrew L.</creatorcontrib><description>Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4⁺ T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.</description><identifier>ISSN: 0022-1899</identifier><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiq095</identifier><identifier>PMID: 21282196</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Antigens ; Biological and medical sciences ; CD4-Positive T-Lymphocytes ; Cytokines ; Cytokines - drug effects ; Dendritic cells ; Disease Models, Animal ; Fundamental and applied biological sciences. Psychology ; Host-Parasite Interactions ; Immunity ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Infections ; Infectious diseases ; Interleukins ; Leishmania major ; Leishmania major - enzymology ; Leishmania major - immunology ; Leishmaniasis, Cutaneous - drug therapy ; Leishmaniasis, Cutaneous - parasitology ; Life cycle. Host-agent relationship. Pathogenesis ; Lymph Nodes - enzymology ; Lymph Nodes - immunology ; Major and Brief Reports ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microbiology ; Ova ; Parasite hosts ; Parasites ; Protozoa ; Specific Pathogen-Free Organisms ; T lymphocytes ; T-Lymphocyte Subsets</subject><ispartof>The Journal of infectious diseases, 2011-03, Vol.203 (5), p.715-725</ispartof><rights>Copyright © 2011 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-faf978d8039363469c5449ae95aee9c375b5eff471f211095654274a9baac0f23</citedby><cites>FETCH-LOGICAL-c570t-faf978d8039363469c5449ae95aee9c375b5eff471f211095654274a9baac0f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25801800$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25801800$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,1584,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23961547$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21282196$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Makala, Levi H. C.</creatorcontrib><creatorcontrib>Baban, Babak</creatorcontrib><creatorcontrib>Lemos, Henrique</creatorcontrib><creatorcontrib>El-Awady, Ahmed R.</creatorcontrib><creatorcontrib>Chandler, Phillip R.</creatorcontrib><creatorcontrib>Hou, De-Yan</creatorcontrib><creatorcontrib>Munn, David H.</creatorcontrib><creatorcontrib>Mellor, Andrew L.</creatorcontrib><title>Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4⁺ T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.</description><subject>Animals</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes</subject><subject>Cytokines</subject><subject>Cytokines - drug effects</subject><subject>Dendritic cells</subject><subject>Disease Models, Animal</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Host-Parasite Interactions</subject><subject>Immunity</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interleukins</subject><subject>Leishmania major</subject><subject>Leishmania major - enzymology</subject><subject>Leishmania major - immunology</subject><subject>Leishmaniasis, Cutaneous - drug therapy</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Lymph Nodes - enzymology</subject><subject>Lymph Nodes - immunology</subject><subject>Major and Brief Reports</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology</subject><subject>Ova</subject><subject>Parasite hosts</subject><subject>Parasites</subject><subject>Protozoa</subject><subject>Specific Pathogen-Free Organisms</subject><subject>T lymphocytes</subject><subject>T-Lymphocyte Subsets</subject><issn>0022-1899</issn><issn>1537-6613</issn><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEoqVw5AjyBakHQv0Rx_EFqWoLXWklDsDZmvWOt14l9tZ2UPffE5RlW06cZqR55p2Pt6reMvqJUS0ufHBrny-2_p5q-aw6pZTzmnVaP3-Sn1Svct5SShvRqpfVCWe840y3pxUu0ee7AYIHMsA2JnJZCoYRCmZyG3Mhi2EYgy97stqT78UPYw_Fhw1ZRgs9WYR17BEGH5Dwj6K-9vFhv8EAGcnNwy5hzj6G19ULB33GN4d4Vv38cvPj6rZefvu6uLpc1lYqWmoHTqtu3VGhRSuaVlvZNBpQS0DUVii5kuhco5jjbLpetrLhqgG9ArDUcXFWfZ51d-NqwLXFUBL0Zpf8AGlvInjzbyX4O7OJv4ygiisuJ4Hzg0CK9yPmYgafLfY9BIxjNqwVWmsuVTeh9YzaFHNO6I5jGDV_rDGzNWa2ZuLfP93tSP_1YgI-HADI02tdgmCn9iMndMtkox53jOPuvzPfzeg2l5gepWRHWUep-A2KkLJ2</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Makala, Levi H. C.</creator><creator>Baban, Babak</creator><creator>Lemos, Henrique</creator><creator>El-Awady, Ahmed R.</creator><creator>Chandler, Phillip R.</creator><creator>Hou, De-Yan</creator><creator>Munn, David H.</creator><creator>Mellor, Andrew L.</creator><general>Oxford University Press</general><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>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>5PM</scope></search><sort><creationdate>20110301</creationdate><title>Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression</title><author>Makala, Levi H. C. ; Baban, Babak ; Lemos, Henrique ; El-Awady, Ahmed R. ; Chandler, Phillip R. ; Hou, De-Yan ; Munn, David H. ; Mellor, Andrew L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-faf978d8039363469c5449ae95aee9c375b5eff471f211095654274a9baac0f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes</topic><topic>Cytokines</topic><topic>Cytokines - drug effects</topic><topic>Dendritic cells</topic><topic>Disease Models, Animal</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Host-Parasite Interactions</topic><topic>Immunity</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Interleukins</topic><topic>Leishmania major</topic><topic>Leishmania major - enzymology</topic><topic>Leishmania major - immunology</topic><topic>Leishmaniasis, Cutaneous - drug therapy</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Lymph Nodes - enzymology</topic><topic>Lymph Nodes - immunology</topic><topic>Major and Brief Reports</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiology</topic><topic>Ova</topic><topic>Parasite hosts</topic><topic>Parasites</topic><topic>Protozoa</topic><topic>Specific Pathogen-Free Organisms</topic><topic>T lymphocytes</topic><topic>T-Lymphocyte Subsets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Makala, Levi H. C.</creatorcontrib><creatorcontrib>Baban, Babak</creatorcontrib><creatorcontrib>Lemos, Henrique</creatorcontrib><creatorcontrib>El-Awady, Ahmed R.</creatorcontrib><creatorcontrib>Chandler, Phillip R.</creatorcontrib><creatorcontrib>Hou, De-Yan</creatorcontrib><creatorcontrib>Munn, David H.</creatorcontrib><creatorcontrib>Mellor, Andrew L.</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Makala, Levi H. C.</au><au>Baban, Babak</au><au>Lemos, Henrique</au><au>El-Awady, Ahmed R.</au><au>Chandler, Phillip R.</au><au>Hou, De-Yan</au><au>Munn, David H.</au><au>Mellor, Andrew L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>203</volume><issue>5</issue><spage>715</spage><epage>725</epage><pages>715-725</pages><issn>0022-1899</issn><issn>1537-6613</issn><eissn>0022-1899</eissn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4⁺ T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21282196</pmid><doi>10.1093/infdis/jiq095</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2011-03, Vol.203 (5), p.715-725 |
| issn | 0022-1899 1537-6613 0022-1899 1537-6613 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3072725 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; JSTOR All Journals; Alma/SFX Local Collection |
| subjects | Animals Antigens Biological and medical sciences CD4-Positive T-Lymphocytes Cytokines Cytokines - drug effects Dendritic cells Disease Models, Animal Fundamental and applied biological sciences. Psychology Host-Parasite Interactions Immunity Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Infections Infectious diseases Interleukins Leishmania major Leishmania major - enzymology Leishmania major - immunology Leishmaniasis, Cutaneous - drug therapy Leishmaniasis, Cutaneous - parasitology Life cycle. Host-agent relationship. Pathogenesis Lymph Nodes - enzymology Lymph Nodes - immunology Major and Brief Reports Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Microbiology Ova Parasite hosts Parasites Protozoa Specific Pathogen-Free Organisms T lymphocytes T-Lymphocyte Subsets |
| title | Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T11%3A07%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Leishmania%20major%20Attenuates%20Host%20Immunity%20by%20Stimulating%20Local%20Indoleamine%202,3-Dioxygenase%20Expression&rft.jtitle=The%20Journal%20of%20infectious%20diseases&rft.au=Makala,%20Levi%20H.%20C.&rft.date=2011-03-01&rft.volume=203&rft.issue=5&rft.spage=715&rft.epage=725&rft.pages=715-725&rft.issn=0022-1899&rft.eissn=0022-1899&rft.coden=JIDIAQ&rft_id=info:doi/10.1093/infdis/jiq095&rft_dat=%3Cjstor_pubme%3E25801800%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1639992578&rft_id=info:pmid/21282196&rft_jstor_id=25801800&rft_oup_id=10.1093/infdis/jiq095&rfr_iscdi=true |