CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp.
Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion.
Department of Clinic, Surgery and Animal Reproduction, Laboratory of Cellular Immunology, School of Veterinary Science of the São Paulo State University (Faculdade de Medicina Veterinária da Universidade Estadual Paulista "Júlio de Mesquita Filho", FMVA/UNESP), Rua Clóvis Pestana, 793, Araçatuba, São Paulo 16050-680, Brazil.
Kathlenn Liezbeth Oliveira
KL
Silva
Larissa Martins
LM
Melo
Juliana
J
Perosso
Bruna Brito
BB
Oliveira
Paulo Sérgio Patto Dos
PS
Santos
Flávia de Rezende
Fde R
Eugênio
Valéria Marçal Felix de
VM
Lima
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D004283:Dog Diseases / Q000276:immunology / Q000469:parasitology*; D004285:Dogs; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007896:Leishmaniasis / Q000662:veterinary*; D008297:Male; D013154:Spleen / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; D019014:fas Receptor
Cell death; FAS-associated death domain protein; FASL-FAS ligand protein; Leishmania chagasi; Leishmaniasis; TRAIL (TNF-related apoptosis-inducing ligand)