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Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection
Chagas disease is caused by infection with the protozoan Trypanosoma cruzi . CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells af...
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| Published in: | Cell death & disease 2016-05, Vol.7 (5), p.e2232-e2232 |
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| container_title | Cell death & disease |
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| creator | Cabral-Piccin, M P Guillermo, L V C Vellozo, N S Filardy, A A Pereira-Marques, S T Rigoni, T S Pereira-Manfro, W F DosReis, G A Lopes, M F |
| description | Chagas disease is caused by infection with the protozoan
Trypanosoma cruzi
. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute
T. cruzi
infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both
in vitro
and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to
T. cruzi
. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence. |
| doi_str_mv | 10.1038/cddis.2016.135 |
| format | article |
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Trypanosoma cruzi
. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute
T. cruzi
infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both
in vitro
and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to
T. cruzi
. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/cddis.2016.135</identifier><identifier>PMID: 27195678</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/21 ; 14 ; 14/63 ; 631/250/1619/554/1834 ; 631/250/2504/342 ; 631/250/255/1715 ; 631/80/82/23 ; 64 ; 64/60 ; Animals ; Antibodies ; Antibodies, Neutralizing - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Asialoglycoproteins - genetics ; Asialoglycoproteins - immunology ; Biochemistry ; Biomedical and Life Sciences ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - parasitology ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - parasitology ; Cell Biology ; Cell Communication - drug effects ; Cell Culture ; Cell Movement - drug effects ; Cellular biology ; Chagas Disease - drug therapy ; Chagas Disease - genetics ; Chagas Disease - immunology ; Chagas Disease - parasitology ; Coculture Techniques ; Cytokines ; Fas Ligand Protein - antagonists & inhibitors ; Fas Ligand Protein - genetics ; Fas Ligand Protein - immunology ; Gene Expression Regulation ; Host-Parasite Interactions ; Immunity, Cellular - drug effects ; Immunology ; Infections ; Interleukin-12 Subunit p35 - genetics ; Interleukin-12 Subunit p35 - immunology ; Lectins, C-Type - genetics ; Lectins, C-Type - immunology ; Life Sciences ; Lymphocyte Activation ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - parasitology ; Male ; Membrane Proteins - genetics ; Membrane Proteins - immunology ; Mice ; Mice, Inbred BALB C ; Original ; original-article ; Phenotype ; Trypanosoma cruzi - growth & development ; Trypanosoma cruzi - immunology</subject><ispartof>Cell death & disease, 2016-05, Vol.7 (5), p.e2232-e2232</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group May 2016</rights><rights>Copyright © 2016 Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-368e833b880e7701386ee49caaed75f421b566beeff0da050254b346bac75aa13</citedby><cites>FETCH-LOGICAL-c458t-368e833b880e7701386ee49caaed75f421b566beeff0da050254b346bac75aa13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1790013075/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1790013075?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27195678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cabral-Piccin, M P</creatorcontrib><creatorcontrib>Guillermo, L V C</creatorcontrib><creatorcontrib>Vellozo, N S</creatorcontrib><creatorcontrib>Filardy, A A</creatorcontrib><creatorcontrib>Pereira-Marques, S T</creatorcontrib><creatorcontrib>Rigoni, T S</creatorcontrib><creatorcontrib>Pereira-Manfro, W F</creatorcontrib><creatorcontrib>DosReis, G A</creatorcontrib><creatorcontrib>Lopes, M F</creatorcontrib><title>Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Chagas disease is caused by infection with the protozoan
Trypanosoma cruzi
. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute
T. cruzi
infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both
in vitro
and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to
T. cruzi
. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence.</description><subject>13/106</subject><subject>13/21</subject><subject>14</subject><subject>14/63</subject><subject>631/250/1619/554/1834</subject><subject>631/250/2504/342</subject><subject>631/250/255/1715</subject><subject>631/80/82/23</subject><subject>64</subject><subject>64/60</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Asialoglycoproteins - genetics</subject><subject>Asialoglycoproteins - immunology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - parasitology</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - parasitology</subject><subject>Cell Biology</subject><subject>Cell Communication - drug effects</subject><subject>Cell Culture</subject><subject>Cell Movement - drug effects</subject><subject>Cellular biology</subject><subject>Chagas Disease - drug therapy</subject><subject>Chagas Disease - genetics</subject><subject>Chagas Disease - immunology</subject><subject>Chagas Disease - parasitology</subject><subject>Coculture Techniques</subject><subject>Cytokines</subject><subject>Fas Ligand Protein - antagonists & inhibitors</subject><subject>Fas Ligand Protein - genetics</subject><subject>Fas Ligand Protein - immunology</subject><subject>Gene Expression Regulation</subject><subject>Host-Parasite Interactions</subject><subject>Immunity, Cellular - drug effects</subject><subject>Immunology</subject><subject>Infections</subject><subject>Interleukin-12 Subunit p35 - genetics</subject><subject>Interleukin-12 Subunit p35 - immunology</subject><subject>Lectins, C-Type - genetics</subject><subject>Lectins, C-Type - immunology</subject><subject>Life Sciences</subject><subject>Lymphocyte Activation</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - parasitology</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Original</subject><subject>original-article</subject><subject>Phenotype</subject><subject>Trypanosoma cruzi - growth & development</subject><subject>Trypanosoma cruzi - immunology</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNptkc1r4zAQxUXZ0pS21x6LYM9OJcv68GUhZD8h0Et6FrI8ThRiyyvJC-5fv-qmW7KwukgwP715Mw-he0qWlDD1aNvWxWVJqFhSxi_QdUkqWlRK1R_O3gt0F-OB5MMYKbm4QotS0poLqa6RXo1-TD45i9efFd4Wx7kf997OCSLO6qY5Au6NDX7cmx0UPbTOJGix6_tpcGnGyeNtmEcz-Oh7g22YXhx2Qwc2OT_cosvOHCPcvd036Pnrl-36e7F5-vZjvdoUtuIqFUwoUIw1ShGQklCmBEBVW2OglbyrStpwIRqAriOtITzPUTWsEo2xkhtD2Q36dNIdpyZ7tDCkYI56DK43YdbeOP1vZXB7vfO_dFVTKYTIAh_fBIL_OUFM-uCnMGTPmsqaZEtE8kwtT1ReSIwBuvcOlOjXTPSfTPRrJjpnkj88nPt6x_8mkIHHExBzadhBOOv7f8nfpp-aUw</recordid><startdate>20160519</startdate><enddate>20160519</enddate><creator>Cabral-Piccin, M P</creator><creator>Guillermo, L V C</creator><creator>Vellozo, N S</creator><creator>Filardy, A A</creator><creator>Pereira-Marques, S T</creator><creator>Rigoni, T S</creator><creator>Pereira-Manfro, W F</creator><creator>DosReis, G A</creator><creator>Lopes, M F</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20160519</creationdate><title>Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection</title><author>Cabral-Piccin, M P ; Guillermo, L V C ; Vellozo, N S ; Filardy, A A ; Pereira-Marques, S T ; Rigoni, T S ; Pereira-Manfro, W F ; DosReis, G A ; Lopes, M F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-368e833b880e7701386ee49caaed75f421b566beeff0da050254b346bac75aa13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/106</topic><topic>13/21</topic><topic>14</topic><topic>14/63</topic><topic>631/250/1619/554/1834</topic><topic>631/250/2504/342</topic><topic>631/250/255/1715</topic><topic>631/80/82/23</topic><topic>64</topic><topic>64/60</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Neutralizing - 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antagonists & inhibitors</topic><topic>Fas Ligand Protein - genetics</topic><topic>Fas Ligand Protein - immunology</topic><topic>Gene Expression Regulation</topic><topic>Host-Parasite Interactions</topic><topic>Immunity, Cellular - drug effects</topic><topic>Immunology</topic><topic>Infections</topic><topic>Interleukin-12 Subunit p35 - genetics</topic><topic>Interleukin-12 Subunit p35 - immunology</topic><topic>Lectins, C-Type - genetics</topic><topic>Lectins, C-Type - immunology</topic><topic>Life Sciences</topic><topic>Lymphocyte Activation</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - parasitology</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - immunology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Original</topic><topic>original-article</topic><topic>Phenotype</topic><topic>Trypanosoma cruzi - growth & development</topic><topic>Trypanosoma cruzi - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cabral-Piccin, M P</creatorcontrib><creatorcontrib>Guillermo, L V C</creatorcontrib><creatorcontrib>Vellozo, N S</creatorcontrib><creatorcontrib>Filardy, A A</creatorcontrib><creatorcontrib>Pereira-Marques, S T</creatorcontrib><creatorcontrib>Rigoni, T S</creatorcontrib><creatorcontrib>Pereira-Manfro, W F</creatorcontrib><creatorcontrib>DosReis, G A</creatorcontrib><creatorcontrib>Lopes, M F</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cabral-Piccin, M P</au><au>Guillermo, L V C</au><au>Vellozo, N S</au><au>Filardy, A A</au><au>Pereira-Marques, S T</au><au>Rigoni, T S</au><au>Pereira-Manfro, W F</au><au>DosReis, G A</au><au>Lopes, M F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2016-05-19</date><risdate>2016</risdate><volume>7</volume><issue>5</issue><spage>e2232</spage><epage>e2232</epage><pages>e2232-e2232</pages><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Chagas disease is caused by infection with the protozoan
Trypanosoma cruzi
. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute
T. cruzi
infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both
in vitro
and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to
T. cruzi
. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27195678</pmid><doi>10.1038/cddis.2016.135</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 13/106 13/21 14 14/63 631/250/1619/554/1834 631/250/2504/342 631/250/255/1715 631/80/82/23 64 64/60 Animals Antibodies Antibodies, Neutralizing - pharmacology Apoptosis Apoptosis - drug effects Asialoglycoproteins - genetics Asialoglycoproteins - immunology Biochemistry Biomedical and Life Sciences CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - parasitology CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - parasitology Cell Biology Cell Communication - drug effects Cell Culture Cell Movement - drug effects Cellular biology Chagas Disease - drug therapy Chagas Disease - genetics Chagas Disease - immunology Chagas Disease - parasitology Coculture Techniques Cytokines Fas Ligand Protein - antagonists & inhibitors Fas Ligand Protein - genetics Fas Ligand Protein - immunology Gene Expression Regulation Host-Parasite Interactions Immunity, Cellular - drug effects Immunology Infections Interleukin-12 Subunit p35 - genetics Interleukin-12 Subunit p35 - immunology Lectins, C-Type - genetics Lectins, C-Type - immunology Life Sciences Lymphocyte Activation Macrophages - drug effects Macrophages - immunology Macrophages - parasitology Male Membrane Proteins - genetics Membrane Proteins - immunology Mice Mice, Inbred BALB C Original original-article Phenotype Trypanosoma cruzi - growth & development Trypanosoma cruzi - immunology |
| title | Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection |
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