Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection

• Published in: Cell death & disease 2016-05, Vol.7 (5), p.e2232-e2232
• Main Authors: 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
• Format: Article
• Language: English
• 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
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2016.135

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.