Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection
Summary The programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypan...
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description | Summary
The programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD‐L1 and PD‐L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD‐1/PD‐L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi‐infected mice suppressed T‐cell proliferation and this was restored when anti‐PD‐1 and anti‐PD‐L1 antibodies were added. Nevertheless, anti‐PD‐L2 antibody treatment did not re‐establish T‐cell proliferation. PD‐L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin‐10 production increased whereas interferon‐γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD‐1 and PD‐L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi‐infected mice. Besides, PD‐L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD‐L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite. |
doi_str_mv | 10.1111/j.1365-2567.2011.03406.x |
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The programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD‐L1 and PD‐L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD‐1/PD‐L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi‐infected mice suppressed T‐cell proliferation and this was restored when anti‐PD‐1 and anti‐PD‐L1 antibodies were added. Nevertheless, anti‐PD‐L2 antibody treatment did not re‐establish T‐cell proliferation. PD‐L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin‐10 production increased whereas interferon‐γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD‐1 and PD‐L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi‐infected mice. Besides, PD‐L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD‐L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1111/j.1365-2567.2011.03406.x</identifier><identifier>PMID: 21303364</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; arginase ; Arginase - biosynthesis ; Arginase - immunology ; B7-1 Antigen - immunology ; B7-1 Antigen - metabolism ; Blotting, Western ; Cell Separation ; Chagas Disease - immunology ; Chagas Disease - metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; inducible nitric oxide synthase ; macrophage ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - parasitology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Nitric Oxide Synthase Type II - immunology ; Nitric Oxide Synthase Type II - metabolism ; Original ; Programmed Cell Death 1 Ligand 2 Protein ; programmed death ligand 2 ; Trypanosoma cruzi ; Trypanosoma cruzi - immunology</subject><ispartof>Immunology, 2011-05, Vol.133 (1), p.29-40</ispartof><rights>2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd</rights><rights>2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.</rights><rights>Copyright © 2011 Blackwell Publishing Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5996-e312c7f1cc1e8f33feb37dfe817329b11538232a4fbb48f3e6167834b9d8bf733</citedby><cites>FETCH-LOGICAL-c5996-e312c7f1cc1e8f33feb37dfe817329b11538232a4fbb48f3e6167834b9d8bf733</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/PMC3088965/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088965/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21303364$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dulgerian, Laura R.</creatorcontrib><creatorcontrib>Garrido, Vanina V.</creatorcontrib><creatorcontrib>Stempin, Cinthia C.</creatorcontrib><creatorcontrib>Cerbán, Fabio M.</creatorcontrib><title>Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection</title><title>Immunology</title><addtitle>Immunology</addtitle><description>Summary
The programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD‐L1 and PD‐L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD‐1/PD‐L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi‐infected mice suppressed T‐cell proliferation and this was restored when anti‐PD‐1 and anti‐PD‐L1 antibodies were added. Nevertheless, anti‐PD‐L2 antibody treatment did not re‐establish T‐cell proliferation. PD‐L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin‐10 production increased whereas interferon‐γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD‐1 and PD‐L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi‐infected mice. Besides, PD‐L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD‐L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite.</description><subject>Animals</subject><subject>arginase</subject><subject>Arginase - biosynthesis</subject><subject>Arginase - immunology</subject><subject>B7-1 Antigen - immunology</subject><subject>B7-1 Antigen - metabolism</subject><subject>Blotting, Western</subject><subject>Cell Separation</subject><subject>Chagas Disease - immunology</subject><subject>Chagas Disease - metabolism</subject><subject>Disease Models, Animal</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>inducible nitric oxide synthase</subject><subject>macrophage</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - parasitology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Nitric Oxide Synthase Type II - immunology</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Original</subject><subject>Programmed Cell Death 1 Ligand 2 Protein</subject><subject>programmed death ligand 2</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - immunology</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk2P0zAQhiMEYsvCX0CWOHBKsOP4IweQ0IqPlXYFh-VsOck4dZXYwW5Ky8_gF-O0SwWc1hePNc-8Ho_fLEMEFyStN5uCUM7yknFRlJiQAtMK82L_KFudE4-zFcakzkuJ2UX2LMZNOlLM2NPsokwBpbxaZb--Bt8HPY7QoQ70do0G22vXoRIF6OdBbyEiHXrrdARkXTe3W-sdWpDRd9bYlL8Lh0k7H_2oURvmnxbFOezsTg-pAo26DX5a6z6R3Rys69G4bIBgP0GwI7jtkTRw1H6ePTF6iPDifr_Mvn38cHf1Ob_58un66v1N3rK65jlQUrbCkLYlIA2lBhoqOgOSCFrWDSGMypKWujJNUyUAOOFC0qqpO9kYQell9u6kO81Nen6b2gh6UFPqSIeD8tqqfzPOrlXvd4piKWvOksDre4Hgv88Qt2q0sYVh0A78HJXkQqTfYPUDSExkJY5NvfqP3Pg5uDQHRVjFsZClWG6WJypNNsYA5tw1wWpxiNqoxQhqMYJaHKKODlH7VPry71efC_9YIgFvT8APO8DhwcLq-vZ2iehvyHvOEQ</recordid><startdate>201105</startdate><enddate>201105</enddate><creator>Dulgerian, Laura R.</creator><creator>Garrido, Vanina V.</creator><creator>Stempin, Cinthia C.</creator><creator>Cerbán, Fabio M.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><general>Blackwell Science Inc</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>7QR</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201105</creationdate><title>Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection</title><author>Dulgerian, Laura R. ; Garrido, Vanina V. ; Stempin, Cinthia C. ; Cerbán, Fabio M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5996-e312c7f1cc1e8f33feb37dfe817329b11538232a4fbb48f3e6167834b9d8bf733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>arginase</topic><topic>Arginase - biosynthesis</topic><topic>Arginase - immunology</topic><topic>B7-1 Antigen - immunology</topic><topic>B7-1 Antigen - metabolism</topic><topic>Blotting, Western</topic><topic>Cell Separation</topic><topic>Chagas Disease - immunology</topic><topic>Chagas Disease - metabolism</topic><topic>Disease Models, Animal</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>inducible nitric oxide synthase</topic><topic>macrophage</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - parasitology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>Nitric Oxide Synthase Type II - immunology</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Original</topic><topic>Programmed Cell Death 1 Ligand 2 Protein</topic><topic>programmed death ligand 2</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosoma cruzi - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dulgerian, Laura R.</creatorcontrib><creatorcontrib>Garrido, Vanina V.</creatorcontrib><creatorcontrib>Stempin, Cinthia C.</creatorcontrib><creatorcontrib>Cerbán, Fabio M.</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>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dulgerian, Laura R.</au><au>Garrido, Vanina V.</au><au>Stempin, Cinthia C.</au><au>Cerbán, Fabio M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>2011-05</date><risdate>2011</risdate><volume>133</volume><issue>1</issue><spage>29</spage><epage>40</epage><pages>29-40</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>Summary
The programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD‐L1 and PD‐L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD‐1/PD‐L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi‐infected mice suppressed T‐cell proliferation and this was restored when anti‐PD‐1 and anti‐PD‐L1 antibodies were added. Nevertheless, anti‐PD‐L2 antibody treatment did not re‐establish T‐cell proliferation. PD‐L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin‐10 production increased whereas interferon‐γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD‐1 and PD‐L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi‐infected mice. Besides, PD‐L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD‐L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21303364</pmid><doi>10.1111/j.1365-2567.2011.03406.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals arginase Arginase - biosynthesis Arginase - immunology B7-1 Antigen - immunology B7-1 Antigen - metabolism Blotting, Western Cell Separation Chagas Disease - immunology Chagas Disease - metabolism Disease Models, Animal Enzyme-Linked Immunosorbent Assay Female Flow Cytometry inducible nitric oxide synthase macrophage Macrophages - immunology Macrophages - metabolism Macrophages - parasitology Mice Mice, Inbred BALB C Mice, Knockout Nitric Oxide Synthase Type II - immunology Nitric Oxide Synthase Type II - metabolism Original Programmed Cell Death 1 Ligand 2 Protein programmed death ligand 2 Trypanosoma cruzi Trypanosoma cruzi - immunology |
title | Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection |
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