title: Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection.
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.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: M P
authors.initials: MP
authors.lastname: Cabral-Piccin
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: L V C
authors.initials: LV
authors.lastname: Guillermo
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: N S
authors.initials: NS
authors.lastname: Vellozo
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: A A
authors.initials: AA
authors.lastname: Filardy
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: S T
authors.initials: ST
authors.lastname: Pereira-Marques
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: T S
authors.initials: TS
authors.lastname: Rigoni
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: W F
authors.initials: WF
authors.lastname: Pereira-Manfro
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.|Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Rio de Janeiro, RJ, Brazil.
authors.forename: G A
authors.initials: GA
authors.lastname: DosReis
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, CCS-IBCCF, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Lopes
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001212:Asialoglycoproteins / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D018920:Coculture Techniques; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D007111:Immunity, Cellular / Q000187:drug effects*; D053765:Interleukin-12 Subunit p35 / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D053765:Interleukin-12 Subunit p35; D037181:Lectins, C-Type; D008565:Membrane Proteins