title: Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease.
abstract: Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease.
authors.affiliation: Departament de Farmacologia, de Toxicologia, i de Terapèutica, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.
authors.forename: Alhelí
authors.initials: A
authors.lastname: Rodríguez-Cortés
authors.affiliation: Leishmaniasis and Chagas Disease Unit, WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiologıía, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Carrillo
authors.affiliation: Zoetis Inc., La Vall de Bianya, Girona, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Martorell
authors.affiliation: Departament de Farmacologia, de Toxicologia, i de Terapèutica, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.
authors.forename: Felicitat
authors.initials: F
authors.lastname: Todolí
authors.affiliation: Departament de Farmacologia, de Toxicologia, i de Terapèutica, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ojeda
authors.affiliation: Departament de Farmacologia, de Toxicologia, i de Terapèutica, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Martínez-Flórez
authors.affiliation: Zoetis Inc., La Vall de Bianya, Girona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Urniza
authors.affiliation: Leishmaniasis and Chagas Disease Unit, WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiologıía, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Departament de Farmacologia, de Toxicologia, i de Terapèutica, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberola
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D005260:Female; D018314:Leishmania infantum / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008198:Lymph Nodes / Q000469:parasitology / Q000473:pathology; D009928:Organ Specificity; D010271:Parasites / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000469:parasitology / Q000473:pathology
chemical_list: D000913:Antibodies, Protozoan; D015415:Biomarkers; D016207:Cytokines