Dataset Information

Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum.

ABSTRACT: A genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Therefore, we scanned 110,165 single-nucleotide polymorphisms (SNPs), aiming to identify chromosomal regions associated with the leishmanin skin test (LST), lymphocyte proliferation assay (LPA), and cytokine responses to further understand the role played by CMI in the outcome of natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI profiles were identified (LST^-/LPA^-, LST⁺/LPA^-, LST^-/LPA⁺, and LST⁺/LPA⁺), which were not associated with subclinically infected or diseased dogs. LST⁺/LPA⁺ dogs showed increased interferon gamma (IFN-?) and tumor necrosis factor alpha (TNF-?) levels and mild parasitism in the lymph nodes, whereas LST^-/LPA⁺ dogs, in spite of increased IFN-?, also showed increased interleukin-10 (IL-10) and transforming growth factor ? (TGF-?) levels and the highest parasite load in lymph nodes. Low T cell proliferation under low parasite load suggested that L. infantum was not able to induce effective CMI in the early stage of infection. Altogether, genetic markers explained 87%, 16%, 15%, 11%, 0%, and 0% of phenotypic variance in TNF-?, TGF-?, LST, IL-10, IFN-?, and LPA, respectively. GWAS showed that regions associated with TNF-? include the following genes: IL12RB1, JAK3, CCRL2, CCR2, CCR3, and CXCR6, involved in cytokine and chemokine signaling; regions associated with LST, including COMMD5 and SHARPIN, involved in regulation of NF-?B signaling; and regions associated with IL-10, including LTBP1 and RASGRP3, involved in T regulatory lymphocytes differentiation. These findings pinpoint chromosomic regions related to the cell-mediated response that potentially affect the clinical complexity and the parasite replication in canine L. infantum infection.

SUBMITTER: Batista LF

PROVIDER: S-EPMC5116739 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum.

Batista Luís F S LF Utsunomiya Yuri T YT Silva Thaís B F TB Dias Raíssa A RA Tomokane Thaise Y TY Pacheco Acácio D AD da Matta Vânia L R VL Silveira Fernando T FT Marcondes Mary M Nunes Cáris M CM Laurenti Márcia D MD

Infection and immunity 20161118 12

A genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Therefore, we scanned 110,165 single-nucleotide polymorphisms (SNPs), aiming to identify chromosomal regions associated with the leishmanin skin test (LST), lymphocyte proliferation assay (LPA), and cytokine responses to further understand the role played by CMI in the outcome of natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI p ...[more]

PMID: 27736777

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Project description:AimThe point prevalence of ocular lesions due to leishmaniasis was evaluated in 127 dogs living in a municipal shelter placed in a highly endemic area (Sicily, Italy). Moreover, the period prevalence, the type, and prognosis of lesions due to leishmaniasis were evaluated in 132 dogs with ocular pathologies referred to a Veterinary Teaching Hospital (VTH) in the same endemic area over a 3-year period.Materials and methodsAll the dogs were submitted to ophthalmological examination. The diagnosis of leishmaniasis was made by cytological, serological (immune-fluorescent antibody test), and molecular (quantitative polymerase chain reaction) tests.ResultsThe point prevalence of ocular lesions in 45 shelter dogs with leishmaniasis was 71.11% (45/127 dogs). The most frequent ocular lesion was blepharitis (50%) while anterior uveitis was observed in only 9.37% of cases. The period prevalence of ocular lesions due to leishmaniasis in the VTH group was 36.36% (48/132 dogs). In both groups, most of the lesions were bilateral and involved the anterior segment. Anterior uveitis was the most frequent ophthalmic finding in client-owned dogs (37.50%), but it occurred in only 9.37% of the shelter dogs. Keratouveitis often occurred during or after antiprotozoal treatment (14.58%; 7/48). In this study, the healing of eye injury following systemic antiprotozoal treatment was recorded in about half of cases (48%; 12/25 dogs), in which follow-up was possible. In more than 1/3 of cases (36%; 9/25), there was an improvement, but it was necessary to associate a long-term topical treatment; most of them, as well as those who had not responded to systemic therapy (16%; 4/25), had anterior uveitis or keratoconjunctivitis sicca.ConclusionsOcular manifestations involve up to 2/3 of animals affected by canine leishmaniasis and lesions account for over 1/3 of ophthalmic pathologies observed at a referral clinic in an endemic area. The occurrence of anterior uveitis is more frequent in client-owned dogs than in shelter dogs. The onset of keratouveitis during or after antiprotozoal treatment could be attributed to the treatment or to a recurrence of the systemic form. The post-treatment uveal immune reaction, already observed in humans, could explain the difference in the frequency of keratouveitis between client-owned and shelter dogs, which have never been treated.

Dataset Information

Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum.

Publications

Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum.

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