title: Parasite load induces progressive spleen architecture breakage and impairs cytokine mRNA expression in Leishmania infantum-naturally infected dogs.
abstract: Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L. infantum in zoonotic VL. Infected dogs develop progressive disease with a large clinical spectrum. A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome. This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil. Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations. By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42). When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups. Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism. All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response. Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ. TNF showed the best negative correlation (r2 = 0.231; p<0.001). Herein we describe impairment on mRNA cytokine expression in leishmania infected dogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture. We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome.
authors: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Amanda S
authors: AS
authors: Cavalcanti
authors: Laboratório de Pesquisa Clínica em DST-AIDS, Instituto de Pesquisa Clínica Evandro Chagas, Fiocruz, Rio de Janeiro, Brasil.
authors: Marcelo
authors: M
authors: Ribeiro-Alves
authors: Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Luiza de O R
authors: Lde O
authors: Pereira
authors: Centro de Controle de Zoonoses, Secretaria Municipal de Saúde, Cuiabá, Brasil.
authors: Gustavo Leandro
authors: GL
authors: Mestre
authors: Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Anna Beatriz Robottom
authors: AB
authors: Ferreira
authors: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Fernanda N
authors: FN
authors: Morgado
authors: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Mariana C
authors: MC
authors: Boité
authors: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Elisa
authors: E
authors: Cupolillo
authors: Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Milton O
authors: MO
authors: Moraes
authors: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
authors: Renato
authors: R
authors: Porrozzi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D004285:Dogs; D015870:Gene Expression; D056724:Immunity, Humoral; D018836:Inflammation Mediators / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000662:veterinary*; D059208:Parasite Load; D012333:RNA, Messenger; D013154:Spleen / Q000378:metabolism* / Q000469:parasitology* / Q000473:pathology
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger