Immune response dynamics and Lutzomyia longipalpis exposure characterize a biosignature of visceral leishmaniasis susceptibility in a canine cohort.

Autor: Solcà MDS; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil.; Escola de Medicina Veterinária e Zootecnia-Universidade Federal da Bahia, Bahia, Brazil., Arruda MR; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil., Leite BMM; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil., Mota TF; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil., Rebouças MF; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil., de Jesus MS; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil., Amorim LDAF; Instituto de Matemática e Estatística-Universidade Federal da Bahia, Bahia, Brazil., Borges VM; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil., Valenzuela J; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America., Kamhawi S; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America., Veras PST; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil.; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais / INCT-DT, Bahia, Brazil., Fraga DBM; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil.; Escola de Medicina Veterinária e Zootecnia-Universidade Federal da Bahia, Bahia, Brazil.; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais / INCT-DT, Bahia, Brazil., Brodskyn CI; Instituto Gonçalo Moniz-Fundação Oswaldo Cruz, Bahia, Brazil.; Instituto Nacional de Ciência e Tecnologia-Investigação em Imunologia /INCT-III, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2021 Feb 22; Vol. 15 (2), pp. e0009137. Date of Electronic Publication: 2021 Feb 22 (Print Publication: 2021).
DOI: 10.1371/journal.pntd.0009137
Abstrakt: Background: Reports have shown correlations between the immune response to vector saliva and Leishmaniasis outcome. We followed dogs in an endemic area for two years characterizing resistance or susceptibility to canine visceral leishmaniasis (CVL) according to Leishmania infantum diagnosis and clinical development criteria. Then, we aimed to identify a biosignature based on parasite load, serum biological mediators' interactions, and vector exposure intensity associated with CVL resistance and susceptibility.
Methodology/principal Findings: A prospective two-year study was conducted in an area endemic for CVL. Dogs were evaluated at 6-month intervals to determine infection, clinical manifestations, immune profile, and sandfly exposure. CVL resistance or susceptibility was determined upon the conclusion of the study. After two years, 78% of the dogs were infected with L. infantum (53% susceptible and 47% resistant to CVL). Susceptible dogs presented higher splenic parasite load as well as persistence of the parasite during the follow-up, compared to resistant ones. Susceptible dogs also displayed a higher number of correlations among the investigated biological mediators, before and after infection diagnosis. At baseline, anti-saliva antibodies, indicative of exposure to the vector, were detected in 62% of the dogs, reaching 100% in one year. Higher sandfly exposure increased the risk of susceptibility to CVL by 1.6 times (CI: 1.11-2.41). We identified a discriminatory biosignature between the resistant and susceptible dogs assessing splenic parasite load, interaction of biological mediators, PGE2 serum levels and intensity of exposure to sandfly. All these parameters were elevated in susceptible dogs compared to resistant animals.
Conclusions/significance: The biosignature identified in our study reinforces the idea that CVL is a complex multifactorial disease that is affected by a set of factors which are correlated and, for a better understanding of CVL, should not be evaluated in an isolated way.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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