{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:09:49Z","timestamp":1771661389683,"version":"3.50.1"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chagas disease is caused by infection with the protozoan <jats:italic>Trypanosoma cruzi<\/jats:italic>. 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 <jats:italic>T. cruzi<\/jats:italic> 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 <jats:italic>in vitro<\/jats:italic> 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 <jats:italic>T. cruzi<\/jats:italic>. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence.<\/jats:p>","DOI":"10.1038\/cddis.2016.135","type":"journal-article","created":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T00:22:26Z","timestamp":1463790146000},"page":"e2232-e2232","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection"],"prefix":"10.1038","volume":"7","author":[{"given":"M P","family":"Cabral-Piccin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L V C","family":"Guillermo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N S","family":"Vellozo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A A","family":"Filardy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S T","family":"Pereira-Marques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T S","family":"Rigoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W F","family":"Pereira-Manfro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G A","family":"DosReis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M F","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"BFcddis2016135_CR1","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1038\/nature09221","volume":"465","author":"JR Coura","year":"2010","unstructured":"Coura JR, Vinas PA . Chagas disease: a new worldwide challenge. Nature 2010; 465: S6\u2013S7.","journal-title":"Nature"},{"key":"BFcddis2016135_CR2","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/S1473-3099(10)70098-0","volume":"10","author":"FX Lescure","year":"2010","unstructured":"Lescure FX, Le Loup G, Freilij H, Develoux M, Paris L, Brutus L et al. Chagas disease: changes in knowledge and management. Lancet Infect Dis 2010; 10: 556\u2013570.","journal-title":"Lancet Infect Dis"},{"key":"BFcddis2016135_CR3","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1056\/NEJMoa1507574","volume":"373","author":"CA Morillo","year":"2015","unstructured":"Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr., Rosas F et al. Randomized Trial of benznidazole for chronic chagas' cardiomyopathy. N Engl J Med 2015; 373: 1295\u20131306.","journal-title":"N Engl J Med"},{"key":"BFcddis2016135_CR4","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1017\/S1462399410001560","volume":"12","author":"C Junqueira","year":"2010","unstructured":"Junqueira C, Caetano B, Bartholomeu DC, Melo MB, Ropert C, Rodrigues MM et al. The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease. Expert Rev Mol Med 2010; 12: e29.","journal-title":"Expert Rev Mol Med"},{"key":"BFcddis2016135_CR5","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1128\/iai.64.6.1961-1967.1996","volume":"64","author":"JC Aliberti","year":"1996","unstructured":"Aliberti JC, Cardoso MA, Martins GA, Gazzinelli RT, Vieira LQ, Silva JS . Interleukin-12 mediates resistance to Trypanosoma cruzi in mice and is produced by murine macrophages in response to live trypomastigotes. Infect Immun 1996; 64: 1961\u20131967.","journal-title":"Infect Immun"},{"key":"BFcddis2016135_CR6","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.4049\/jimmunol.177.6.3515","volume":"177","author":"A Bafica","year":"2006","unstructured":"Bafica A, Santiago HC, Goldszmid R, Ropert C, Gazzinelli RT, Sher A . Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J Immunol 2006; 177: 3515\u20133519.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR7","doi-asserted-by":"publisher","first-page":"507874","DOI":"10.1155\/2012\/507874","volume":"2012","author":"MM Rodrigues","year":"2012","unstructured":"Rodrigues MM, Oliveira AC, Bellio M . The immune response to Trypanosoma cruzi: role of Toll-like receptors and perspectives for vaccine development. J Parasitol Res 2012; 2012: 507874.","journal-title":"J Parasitol Res"},{"key":"BFcddis2016135_CR8","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.2217\/fmb.11.122","volume":"6","author":"A Pellegrini","year":"2011","unstructured":"Pellegrini A, Guinazu N, Giordanengo L, Cano RC, Gea S . The role of Toll-like receptors and adaptive immunity in the development of protective or pathological immune response triggered by the Trypanosoma cruzi protozoan. Fut Microbiol 2011; 6: 1521\u20131533.","journal-title":"Fut Microbiol"},{"key":"BFcddis2016135_CR9","doi-asserted-by":"publisher","first-page":"6166","DOI":"10.4049\/jimmunol.164.12.6166","volume":"164","author":"CD Mills","year":"2000","unstructured":"Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM . M-1\/M-2 macrophages and the Th1\/Th2 paradigm. J Immunol 2000; 164: 6166\u20136173.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1189\/jlb.71.2.271","volume":"71","author":"KR Bastos","year":"2002","unstructured":"Bastos KR, Alvarez JM, Marinho CR, Rizzo LV, Lima MR . Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile. J Leukoc Biol 2002; 71: 271\u2013278.","journal-title":"J Leukoc Biol"},{"key":"BFcddis2016135_CR11","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","volume":"23","author":"A Mantovani","year":"2002","unstructured":"Mantovani A, Sozzani S, Locati M, Allavena P, Sica A . Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23: 549\u2013555.","journal-title":"Trends Immunol"},{"key":"BFcddis2016135_CR12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","volume":"41","author":"PJ Murray","year":"2014","unstructured":"Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41: 14\u201320.","journal-title":"Immunity"},{"key":"BFcddis2016135_CR13","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/356338a0","volume":"356","author":"RL Tarleton","year":"1992","unstructured":"Tarleton RL, Koller BH, Latour A, Postan M . Susceptibility of b2-microglobulin-deficient mice to Trypanosoma cruzi infection. Nature 1992; 356: 338\u2013340.","journal-title":"Nature"},{"key":"BFcddis2016135_CR14","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1128\/iai.61.12.5129-5133.1993","volume":"61","author":"ME Rottenberg","year":"1993","unstructured":"Rottenberg ME, Bakhiet M, Olsson T, Kristensson K, Mak T, Wigzell H et al. Differential susceptibilities of mice genomically deleted of CD4 and CD8 to infections with Trypanosoma cruzi or Trypanosoma brucei. Infect Immun 1993; 61: 5129\u20135133.","journal-title":"Infect Immun"},{"key":"BFcddis2016135_CR15","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1046\/j.1365-3024.1998.00154.x","volume":"20","author":"S Kumar","year":"1998","unstructured":"Kumar S, Tarleton RL . The relative contribution of antibody production and CD8+ T cell function to immune control of Trypanosoma cruzi. Parasite Immunol 1998; 20: 207\u2013216.","journal-title":"Parasite Immunol"},{"key":"BFcddis2016135_CR16","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.4049\/jimmunol.150.4.1446","volume":"150","author":"SP Nickell","year":"1993","unstructured":"Nickell SP, Stryker GA, Arevalo C . Isolation from Trypanosoma cruzi-infected mice of CD8+, MHC-restricted cytotoxic T cells that lyse parasite-infected target cells. J Immunol 1993; 150: 1446\u20131457.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR17","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1006\/expr.2000.4498","volume":"94","author":"SP Nickell","year":"2000","unstructured":"Nickell SP, Sharma D . Trypanosoma cruzi: roles for perforin-dependent and perforin-independent immune mechanisms in acute resistance. Exp Parasitol 2000; 94: 207\u2013216.","journal-title":"Exp Parasitol"},{"key":"BFcddis2016135_CR18","doi-asserted-by":"publisher","first-page":"e1002645","DOI":"10.1371\/journal.ppat.1002645","volume":"8","author":"JC Silverio","year":"2012","unstructured":"Silverio JC, Pereira IR, Cipitelli Mda C, Vinagre NF, Rodrigues MM, Gazzinelli RT et al. CD8+ T-cells expressing interferon gamma or perforin play antagonistic roles in heart injury in experimental Trypanosoma cruzi-elicited cardiomyopathy. PLoS Pathog 2012; 8: e1002645.","journal-title":"PLoS Pathog"},{"key":"BFcddis2016135_CR19","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1093\/intimm\/dxh387","volume":"18","author":"MC Albareda","year":"2006","unstructured":"Albareda MC, Laucella SA, Alvarez MG, Armenti AH, Bertochi G, Tarleton RL et al. Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas' disease patients. Int Immunol 2006; 18: 465\u2013471.","journal-title":"Int Immunol"},{"key":"BFcddis2016135_CR20","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.it.2007.06.004","volume":"28","author":"MF Lopes","year":"2007","unstructured":"Lopes MF, Guillermo LV, Silva EM . Decoding caspase signaling in host immunity to the protozoan Trypanosoma cruzi. Trends Immunol 2007; 28: 366\u2013372.","journal-title":"Trends Immunol"},{"key":"BFcddis2016135_CR21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.cytogfr.2007.01.009","volume":"18","author":"GA DosReis","year":"2007","unstructured":"DosReis GA, Ribeiro-Gomes FL, Guillermo LV, Lopes MF . Cross-talk between apoptosis and cytokines in the regulation of parasitic infection. Cytokine Growth Factor Rev 2007; 18: 97\u2013105.","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFcddis2016135_CR22","doi-asserted-by":"crossref","first-page":"744","DOI":"10.4049\/jimmunol.154.2.744","volume":"154","author":"MF Lopes","year":"1995","unstructured":"Lopes MF, da Veiga VF, Santos AR, Fonseca ME, DosReis GA . Activation-induced CD4+ T cell death by apoptosis in experimental Chagas' disease. J Immunol 1995; 154: 744\u2013752.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<81::AID-IMMU81>3.0.CO;2-Y","volume":"29","author":"MF Lopes","year":"1999","unstructured":"Lopes MF, Nunes MP, Henriques-Pons A, Giese N, Morse HC III, Davidson WF et al. Increased susceptibility of Fas ligand-deficient gld mice to Trypanosoma cruzi infection due to a Th2-biased host immune response. Eur J Immunol 1999; 29: 81\u201389.","journal-title":"Eur J Immunol"},{"key":"BFcddis2016135_CR24","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1046\/j.1365-2249.2000.01150.x","volume":"119","author":"E Zuniga","year":"2000","unstructured":"Zuniga E, Motran C, Montes CL, Diaz FL, Bocco JL, Gruppi A . Trypanosoma cruzi-induced immunosuppression: B cells undergo spontaneous apoptosis and lipopolysaccharide (LPS) arrests their proliferation during acute infection. Clin Exp Immunol 2000; 119: 507\u2013515.","journal-title":"Clin Exp Immunol"},{"key":"BFcddis2016135_CR25","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.4049\/jimmunol.160.3.1313","volume":"160","author":"MP Nunes","year":"1998","unstructured":"Nunes MP, Andrade RM, Lopes MF, DosReis GA . Activation-induced T cell death exacerbates Trypanosoma cruzi replication in macrophages cocultured with CD4+ T lymphocytes from infected hosts. J Immunol 1998; 160: 1313\u20131319.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR26","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1189\/jlb.1006643","volume":"81","author":"LV Guillermo","year":"2007","unstructured":"Guillermo LV, Silva EM, Ribeiro-Gomes FL, De Meis J, Pereira WF, Yagita H et al. The Fas death pathway controls coordinated expansions of type 1 CD8 and type 2 CD4 T cells in Trypanosoma cruzi infection. J Leukoc Biol 2007; 81: 942\u2013951.","journal-title":"J Leukoc Biol"},{"key":"BFcddis2016135_CR27","doi-asserted-by":"publisher","first-page":"e1002699","DOI":"10.1371\/journal.ppat.1002699","volume":"8","author":"JR Vasconcelos","year":"2012","unstructured":"Vasconcelos JR, Bruna-Romero O, Araujo AF, Dominguez MR, Ersching J, de Alencar BC et al. Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8+ T-cell response: reversal by adenoviral vaccine. PLoS Pathog 2012; 8: e1002699.","journal-title":"PLoS Pathog"},{"key":"BFcddis2016135_CR28","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/35003208","volume":"403","author":"CG Freire-de-Lima","year":"2000","unstructured":"Freire-de-Lima CG, Nascimento DO, Soares MB, Bozza PT, Castro-Faria-Neto HC, de Mello FG et al. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature 2000; 403: 199\u2013203.","journal-title":"Nature"},{"key":"BFcddis2016135_CR29","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1002\/eji.200636790","volume":"37","author":"EM Silva","year":"2007","unstructured":"Silva EM, Guillermo LV, Ribeiro-Gomes FL, De Meis J, Nunes MP, Senra JF et al. Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection. Eur J Immunol 2007; 37: 738\u2013746.","journal-title":"Eur J Immunol"},{"key":"BFcddis2016135_CR30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1080\/08923970802332164","volume":"31","author":"LV Guillermo","year":"2009","unstructured":"Guillermo LV, Pereira WF, De Meis J, Ribeiro-Gomes FL, Silva EM, Kroll-Palhares K et al. Targeting caspases in intracellular protozoan infections. Immunopharmacol Immunotoxicol 2009; 31: 159\u2013173.","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"BFcddis2016135_CR31","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/nri3607","volume":"14","author":"IK Poon","year":"2014","unstructured":"Poon IK, Lucas CD, Rossi AG, Ravichandran KS . Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 2014; 14: 166\u2013180.","journal-title":"Nat Rev Immunol"},{"key":"BFcddis2016135_CR32","doi-asserted-by":"publisher","first-page":"6314","DOI":"10.4049\/jimmunol.174.10.6314","volume":"174","author":"EM Silva","year":"2005","unstructured":"Silva EM, Guillermo LV, Ribeiro-Gomes FL, De Meis J, Pereira RM, Wu Z et al. Caspase-8 activity prevents type 2 cytokine responses and is required for protective T cell-mediated immunity against Trypanosoma cruzi infection. J Immunol 2005; 174: 6314\u20136321.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR33","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1006\/expr.1995.1024","volume":"80","author":"MF Lopes","year":"1995","unstructured":"Lopes MF, Cunha JM, Bezerra FL, Gonzalez MS, Gomes JE, Lapa e Silva JR et al. Trypanosoma cruzi: both chemically induced and triatomine-derived metacyclic trypomastigotes cause the same immunological disturbances in the infected mammalian host. Exp Parasitol 1995; 80: 194\u2013204.","journal-title":"Exp Parasitol"},{"key":"BFcddis2016135_CR34","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1111\/j.1365-3083.2007.01987.x","volume":"66","author":"SG Fonseca","year":"2007","unstructured":"Fonseca SG, Reis MM, Coelho V, Nogueira LG, Monteiro SM, Mairena EC et al. Locally produced survival cytokines IL-15 and IL-7 may be associated to the predominance of CD8+ T cells at heart lesions of human chronic Chagas disease cardiomyopathy. Scand J Immunol 2007; 66: 362\u2013371.","journal-title":"Scand J Immunol"},{"key":"BFcddis2016135_CR35","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.4049\/jimmunol.180.3.1737","volume":"180","author":"F Tzelepis","year":"2008","unstructured":"Tzelepis F, de Alencar BC, Penido ML, Claser C, Machado AV, Bruna-Romero O et al. Infection with Trypanosoma cruzi restricts the repertoire of parasite-specific CD8+ T cells leading to immunodominance. J Immunol 2008; 180: 1737\u20131748.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR36","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1189\/jlb.0304212","volume":"77","author":"G Raes","year":"2005","unstructured":"Raes G, Brys L, Dahal BK, Brandt J, Grooten J, Brombacher F et al. Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation. J Leukoc Biol 2005; 77: 321\u2013327.","journal-title":"J Leukoc Biol"},{"key":"BFcddis2016135_CR37","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.4049\/jimmunol.1002928","volume":"187","author":"H Cuervo","year":"2011","unstructured":"Cuervo H, Guerrero NA, Carbajosa S, Beschin A, De Baetselier P, Girones N et al. Myeloid-derived suppressor cells infiltrate the heart in acute Trypanosoma cruzi infection. J Immunol 2011; 187: 2656\u20132665.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR38","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.4049\/jimmunol.1203293","volume":"191","author":"GK Silva","year":"2013","unstructured":"Silva GK, Costa RS, Silveira TN, Caetano BC, Horta CV, Gutierrez FR et al. Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1beta response and host resistance to Trypanosoma cruzi infection. J Immunol 2013; 191: 3373\u20133383.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR39","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1002\/eji.200737041","volume":"37","author":"E Kuroda","year":"2007","unstructured":"Kuroda E, Noguchi J, Doi T, Uematsu S, Akira S, Yamashita U . IL-3 is an important differentiation factor for the development of prostaglandin E2-producing macrophages between C57BL\/6 and BALB\/c mice. Eur J Immunol 2007; 37: 2185\u20132195.","journal-title":"Eur J Immunol"},{"key":"BFcddis2016135_CR40","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.4049\/jimmunol.160.11.5347","volume":"160","author":"M Munder","year":"1998","unstructured":"Munder M, Eichmann K, Modolell M . Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase\/arginase balance: competitive regulation by CD4+ T cells correlates with Th1\/Th2 phenotype. J Immunol 1998; 160: 5347\u20135354.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR41","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1084\/jem.20140964","volume":"212","author":"MR Jenkins","year":"2015","unstructured":"Jenkins MR, Rudd-Schmidt JA, Lopez JA, Ramsbottom KM, Mannering SI, Andrews DM et al. Failed CTL\/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time. J Exp Med 2015; 212: 307\u2013317.","journal-title":"J Exp Med"},{"key":"BFcddis2016135_CR42","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.immuni.2009.06.018","volume":"31","author":"N A-Gonzalez","year":"2009","unstructured":"A-Gonzalez N, Bensinger SJ, Hong C, Beceiro S, Bradley MN, Zelcer N et al. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 2009; 31: 245\u2013258.","journal-title":"Immunity"},{"key":"BFcddis2016135_CR43","first-page":"ra13","volume":"3","author":"F Li","year":"2010","unstructured":"Li F, Huang Q, Chen J, Peng Y, Roop DR, Bedford JS et al. Apoptotic cells activate the 'phoenix rising' pathway to promote wound healing and tissue regeneration. Sci Signal 2010; 3: ra13.","journal-title":"Sci Signal"},{"key":"BFcddis2016135_CR44","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1189\/jlb.1008590","volume":"86","author":"R Chakour","year":"2009","unstructured":"Chakour R, Allenbach C, Desgranges F, Charmoy M, Mauel J, Garcia I et al. A new function of the Fas-FasL pathway in macrophage activation. J Leukoc Biol 2009; 86: 81\u201390.","journal-title":"J Leukoc Biol"},{"key":"BFcddis2016135_CR45","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<237::AID-IMMU237>3.0.CO;2-O","volume":"28","author":"F Conceicao-Silva","year":"1998","unstructured":"Conceicao-Silva F, Hahne M, Schroter M, Louis J, Tschopp J . The resolution of lesions induced by Leishmania major in mice requires a functional Fas (APO-1, CD95) pathway of cytotoxicity. Eur J Immunol 1998; 28: 237\u2013245.","journal-title":"Eur J Immunol"},{"key":"BFcddis2016135_CR46","doi-asserted-by":"publisher","first-page":"4454","DOI":"10.4049\/jimmunol.172.7.4454","volume":"172","author":"FL Ribeiro-Gomes","year":"2004","unstructured":"Ribeiro-Gomes FL, Otero AC, Gomes NA, Moniz-De-Souza MC, Cysne-Finkelstein L, Arnholdt AC et al. Macrophage interactions with neutrophils regulate Leishmania major infection. J Immunol 2004; 172: 4454\u20134462.","journal-title":"J Immunol"},{"key":"BFcddis2016135_CR47","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/82741","volume":"1","author":"RS Hotchkiss","year":"2000","unstructured":"Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P et al. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol 2000; 1: 496\u2013501.","journal-title":"Nat Immunol"},{"key":"BFcddis2016135_CR48","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1084\/jem.20082058","volume":"206","author":"AI Medeiros","year":"2009","unstructured":"Medeiros AI, Serezani CH, Lee SP, Peters-Golden M . Efferocytosis impairs pulmonary macrophage and lung antibacterial function via PGE2\/EP2 signaling. J Exp Med 2009; 206: 61\u201368.","journal-title":"J Exp Med"},{"key":"BFcddis2016135_CR49","doi-asserted-by":"publisher","first-page":"e1000066","DOI":"10.1371\/journal.ppat.1000066","volume":"4","author":"M Benoit","year":"2008","unstructured":"Benoit M, Ghigo E, Capo C, Raoult D, Mege JL . The uptake of apoptotic cells drives Coxiella burnetii replication and macrophage polarization: a model for Q fever endocarditis. PLoS Pathog 2008; 4: e1000066.","journal-title":"PLoS Pathog"},{"key":"BFcddis2016135_CR50","doi-asserted-by":"publisher","first-page":"3968","DOI":"10.1128\/IAI.02194-14","volume":"82","author":"T de Oliveira Fulco","year":"2014","unstructured":"de Oliveira Fulco T, Andrade PR, de Mattos Barbosa MG, Pinto TG, Ferreira PF, Ferreira H et al. Effect of apoptotic cell recognition on macrophage polarization and mycobacterial persistence. Infect Immun 2014; 82: 3968\u20133978.","journal-title":"Infect Immun"},{"key":"BFcddis2016135_CR51","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1089\/aid.2006.22.763","volume":"22","author":"RG Lima","year":"2006","unstructured":"Lima RG, Moreira L, Paes-Leme J, Barreto-de-Souza V, Castro-Faria-Neto HC, Bozza PT et al. Interaction of macrophages with apoptotic cells enhances HIV Type 1 replication through PGE2, PAF, and vitronectin receptor. AIDS Res Hum Retrov 2006; 22: 763\u2013769.","journal-title":"AIDS Res Hum Retrov"},{"key":"BFcddis2016135_CR52","doi-asserted-by":"publisher","first-page":"e1002536","DOI":"10.1371\/journal.ppat.1002536","volume":"8","author":"FL Ribeiro-Gomes","year":"2012","unstructured":"Ribeiro-Gomes FL, Peters NC, Debrabant A, Sacks DL . Efficient capture of infected neutrophils by dendritic cells in the skin inhibits the early anti-leishmania response. PLoS Pathog 2012; 8: e1002536.","journal-title":"PLoS Pathog"},{"key":"BFcddis2016135_CR53","doi-asserted-by":"publisher","first-page":"e2018","DOI":"10.1038\/cddis.2015.351","volume":"6","author":"FL Ribeiro-Gomes","year":"2015","unstructured":"Ribeiro-Gomes FL, Romano A, Lee S, Roffe E, Peters NC, Debrabant A et al. Apoptotic cell clearance of Leishmania major-infected neutrophils by dendritic cells inhibits CD8(+) T-cell priming in vitro by Mer tyrosine kinase-dependent signaling. Cell Death Dis 2015; 6: e2018.","journal-title":"Cell Death Dis"},{"key":"BFcddis2016135_CR54","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.chom.2012.06.010","volume":"12","author":"CJ Martin","year":"2012","unstructured":"Martin CJ, Booty MG, Rosebrock TR, Nunes-Alves C, Desjardins DM, Keren I et al. Efferocytosis is an innate antibacterial mechanism. Cell Host Microbe 2012; 12: 289\u2013300.","journal-title":"Cell Host Microbe"},{"key":"BFcddis2016135_CR55","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/ni.2986","volume":"15","author":"A Zagorska","year":"2014","unstructured":"Zagorska A, Traves PG, Lew ED, Dransfield I, Lemke G . Diversification of TAM receptor tyrosine kinase function. Nat Immunol 2014; 15: 920\u2013928.","journal-title":"Nat Immunol"},{"key":"BFcddis2016135_CR56","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.imbio.2015.01.013","volume":"220","author":"KJ Mylonas","year":"2015","unstructured":"Mylonas KJ, Jenkins SJ, Castellan RF, Ruckerl D, McGregor K, Phythian-Adams AT et al. The adult murine heart has a sparse, phagocytically active macrophage population that expands through monocyte recruitment and adopts an 'M2' phenotype in response to Th2 immunologic challenge. Immunobiology 2015; 220: 924\u2013933.","journal-title":"Immunobiology"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2016135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016135","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T09:09:18Z","timestamp":1672823358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2016135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,19]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,5]]}},"alternative-id":["BFcddis2016135"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.135","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,19]]},"assertion":[{"value":"18 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}