Circulating Biomarkers of Immune Activation, Oxidative Stress and Inflammation Characterize Severe Canine Visceral Leishmaniasis.
Clinical manifestations in canine visceral leishmaniasis (CVL) have not been clearly associated with immunological status or disease progression. We simultaneously assessed biomarkers of inflammation, immune activation, oxidative stress, and anti-sand fly saliva IgG concentrations in dog sera with different clinical manifestations to characterize a biosignature associated with CVL severity. In a cross-sectional exploratory study, a random population of 70 dogs from an endemic area in Brazil was classified according to CVL clinical severity and parasitological evaluation. A panel of biomarkers and anti-sand fly saliva IgG were measured in canine sera. Assessment of protein expression of profile biomarkers identified a distinct biosignature that could cluster separately animal groups with different clinical scores. Increasing severity scores were associated with a gradual decrease of LTB4 and PGE2, and a gradual increase in CXCL1 and CCL2. Discriminant analyses revealed that combined assessment of LTB4, PGE2 and CXCL1 was able to distinguish dogs with different clinical scores. Dogs with the highest clinical score values also exhibited high parasite loads and higher concentrations of anti-saliva antibodies. Our findings suggest CVL clinical severity is tightly associated with a distinct inflammatory profile hallmarked by a differential expression of circulating eicosanoids and chemokines.
Laboratório de Patologia e Biointervenção, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.
Manuela S
MS
Solcà
Laboratório Integrado de Microbiologia e Imunoregulação, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, 40070-080 Salvador, Brazil.
Bruno B
BB
Andrade
Laboratório Integrado de Microbiologia e Imunoregulação, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.
Melissa Moura Costa
MM
Abbehusen
Fundação Oswaldo Cruz, Fiocruz Piauí, 64128 Teresina, Brazil.
Clarissa R
CR
Teixeira
Laboratório Integrado de Microbiologia e Imunoregulação, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.
Ricardo
R
Khouri
Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD, 20852, USA.
Jesus G
JG
Valenzuela
Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD, 20852, USA.
Shaden
S
Kamhawi
Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Bio-Manguinhos, FIOCRUZ, 21040-900 Rio de Janeiro, Brazil.
Patrícia Torres
PT
Bozza
Laboratório de Patologia e Biointervenção, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.|Departamento de Medicina Veterinária Preventiva e Produção Animal, Escola de Medicina Veterinária e Zootecnia, Universidade Federal da Bahia, 40170-110 Salvador, Brazil.|Instituto Nacional de Ciência e Tecnologia para Doenças Tropicais (INCT-DT), 40110-160 Salvador, Brazil.
Deborah Bittencourt Mothé
DB
Fraga
Laboratório Integrado de Microbiologia e Imunoregulação, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.
Valeria Matos
VM
Borges
Laboratório de Patologia e Biointervenção, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.|Instituto Nacional de Ciência e Tecnologia para Doenças Tropicais (INCT-DT), 40110-160 Salvador, Brazil.
Patrícia Sampaio Tavares
PS
Veras
Laboratório Integrado de Microbiologia e Imunoregulação, Instituto de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, Brazil.|Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (III-INCT), 05403-900 São Paulo, Brazil.
Claudia Ida
CI
Brodskyn
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D004283:Dog Diseases / Q000097:blood* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D053263:Gene Regulatory Networks; D007249:Inflammation / Q000097:blood* / Q000235:genetics / Q000473:pathology; D007898:Leishmaniasis, Visceral / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D018384:Oxidative Stress; D010271:Parasites / Q000502:physiology; D012372:ROC Curve; D011994:Recombinant Proteins / Q000378:metabolism; D012463:Saliva / Q000378:metabolism
D000913:Antibodies, Protozoan; D015415:Biomarkers; D011994:Recombinant Proteins