ABSTRACT
Activated Vγ9Vδ2 (γδ2) T lymphocytes that sense parasite-produced phosphoantigens are expanded in Plasmodium falciparum-infected patients. Although previous studies suggested that γδ2 T cells help control erythrocytic malaria, whether γδ2 T cells recognize infected red blood cells (iRBCs) was uncertain. Here we show that iRBCs stained for the phosphoantigen sensor butyrophilin 3A1 (BTN3A1). γδ2 T cells formed immune synapses and lysed iRBCs in a contact, phosphoantigen, BTN3A1 and degranulation-dependent manner, killing intracellular parasites. Granulysin released into the synapse lysed iRBCs and delivered death-inducing granzymes to the parasite. All intra-erythrocytic parasites were susceptible, but schizonts were most sensitive. A second protective γδ2 T cell mechanism was identified. In the presence of patient serum, γδ2 T cells phagocytosed and degraded opsonized iRBCs in a CD16-dependent manner, decreasing parasite multiplication. Thus, γδ2 T cells have two ways to control blood-stage malaria-γδ T cell antigen receptor (TCR)-mediated degranulation and phagocytosis of antibody-coated iRBCs.
Subject(s)
Antigens, Protozoan/immunology , Cytotoxicity, Immunologic , Erythrocytes/immunology , Intraepithelial Lymphocytes/immunology , Lymphocyte Activation , Malaria, Falciparum/immunology , Phagocytosis , Plasmodium falciparum/microbiology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Antigens, Protozoan/blood , Boston , Brazil , Butyrophilins/metabolism , Cells, Cultured , Erythrocytes/metabolism , Erythrocytes/parasitology , Female , Granzymes/metabolism , Host-Parasite Interactions , Humans , Immunological Synapses/metabolism , Immunological Synapses/parasitology , Intraepithelial Lymphocytes/metabolism , Intraepithelial Lymphocytes/parasitology , Malaria, Falciparum/blood , Malaria, Falciparum/parasitology , Male , Plasmodium falciparum/growth & developmentABSTRACT
Many kinds of lymphocytes are involved in Schistosoma japonicum (S. japonicum) infection-induced disease. γδ T cells comprise a small number of innate lymphocytes that quickly respond to foreign materials. In this study, the role of γδ T cells in the lung of S. japonicum-infected C56BL/6 mice was investigated. The results demonstrated that S. japonicum infection induces γδ T cell accumulation in the lung, expressing higher levels of CD25, MHCII, CD80, and PDL1, and lower levels of CD127 and CD62L (P < 0.05). The intracellular cytokines staining results illustrated higher percentages of IL-4-, IL-10-, IL-21-, and IL-6-producing γδ T cells and lower percentages of IFN-γ-expressing γδ T cells in the lung of infected mice (P < 0.05). Moreover, the granuloma size in lung tissue was significantly increased in Vδ-/- mice (P < 0.05). In the lung of S. japonicum-infected Vδ-/- mice, both type 1 and type 2 immune responses were decreased significantly (P < 0.05). In addition, the expression of CD80 and CD69 on B cells was decreased significantly (P < 0.05), and the SEA-specific antibody was markedly decreased (P < 0.05) in the blood of infected Vδ-/- mice. In conclusion, this study indicates that γδ T cells could adjust the Th2 dominant immune response in the lung of S. japonicum-infected mice.
Subject(s)
Intraepithelial Lymphocytes/immunology , Intraepithelial Lymphocytes/parasitology , Lung/immunology , Lung/parasitology , Schistosomiasis japonica/immunology , Animals , B-Lymphocytes/immunology , Cytokines/metabolism , Disease Models, Animal , Female , Genes, T-Cell Receptor delta , Immunity, Innate , Immunophenotyping , Lung/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Antigen, T-Cell, gamma-delta/deficiency , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/immunology , Schistosoma japonicum/immunology , Schistosoma japonicum/pathogenicity , Schistosomiasis japonica/parasitology , Schistosomiasis japonica/pathologyABSTRACT
Proinflammatory IL-17 plays an important role in various diseases and defence against extracellular microorganisms. Healing of leishmaniasis is promoted by Th1/Tc1 cells, whereas Th2/Treg are associated with worsened disease outcome. In addition, high expression of IL-17A in Leishmania-susceptible BALB/c and artificial overexpression of IL-17A in T cells in resistant C57BL/6 mice worsened disease outcome. Since C57BL/6 mice lacking only IL-17A exhibited no phenotype, and IL-17A and IL-17F share similar receptors, but differentially regulate chemokine secretion, we studied mice lacking both IL-17A and IL-17F (IL-17A/F-/- ) in infections with Leishmania major. Interestingly, lesion volumes and parasite burdens were comparable to controls, IL-17A/F-/- mice developed a Th1/Tc1 phenotype, and exhibited normal lesion resolution. Thus, in C57BL/6 mice, secretion of IL-17A and IL-17F does not influence disease progression. It appears that-depending on the genetic background-cytokines of the IL-17 family might be responsible for disease progression primarily in susceptible mice.
