PD-1 and PD-L1 regulate cellular immunity in canine visceral leishmaniasis |
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| Affiliation: | 1. Unidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain;2. Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, IBSAL, CIBERehd, Salamanca, Spain;3. VISAVET Health Surveillance Centre, Universidad Complutense de Madrid, Madrid, Spain;1. Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS INRCA, Italy;2. Istituto Zooprofilattico Sperimentale dell’Umbria e delle Marche, Ancona, Italy;3. BHD Holding B.V., Amsterdam, the Netherlands;4. KBLH Holding B.V., Amsterdam, the Netherlands;1. Department of Immunology, Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic;2. Department of Special Microbiology, State Veterinary Institute Olomouc, Jakoubka ze Stribra 1, 779 00 Olomouc, Czech Republic;3. Department of Technology and Breeding Technique of Farm Animals, Institute of Animal Science, Pratelstvi 815, 104 00 Prague, Czech Republic;1. Department of Pathobiology and Population Sciences, Royal Veterinary College, North Mymms, Hertfordshire, AL9 7TA, UK;2. Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, Barcelona, Spain;3. Cyvets Veterinary Center, Paphos, Cyprus;4. Unit of Vector-Borne Diseases, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy;5. Dipartimento di Medicina Veterinaria e Produzioni Animali, Naples University, Naples, Italy;6. Molecular Diagnostic Unit, Diagnostic Laboratories, Langford Vets, University of Bristol, BS40 5DU, UK |
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| Abstract: | PD-1 is a negative costimulator of chronic infectious diseases In this study, we investigated the expression of PD-1 and its ligands in the spleen of dogs with visceral leishmaniasis and lymphoproliferative response to soluble antigen, in lymph node cells in the presence or absence of antibodies blocking PD-1 and its ligands. Our results showed expression of PD-1 and its ligands is higher after L. infantum infection and in the spleen of infected dogs, PD-1 blockage was able to restore the antigen-dependent lymphoproliferative response and regulated production of the cytokines IL-4 and IL-10 and NO production. We concluded that L. infantum infection modulates PD-1 and its ligands expression in canine VL and that blockage of PD-1 restores the immune response. Thus, blockage of PD-1 is a target for therapeutic drug development. |
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| Keywords: | Lymphoproliferation Canine Visceral leishmaniasis PD-1 Cytokine Nitric oxide |
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