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

Batista, Luis Francisco Zirnberger; Utsunomiya, Yuri Tani; Silva, Thaís B.F.; Dias, Raíssa A.; Tomokane, Thaíse Yumie; Pacheco, Acácio Duarte; Matta, Vânia Lúcia Ribeiro da; Sílveira, Fernando Tobias; Marcondes, Mary; Nunes, Cáris Maroni; Laurenti, Márcia Dalastra

doi:10.1128/iai.00486-16

Cited by 12 publications

(7 citation statements)

References 58 publications

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“…Hosts who activate the humoral immune response or Th2 pathway develop the disease with greater prevalence and severity since the antibodies are ineffective and stimulation by cytokines is based on the production of IL-10. This situation favors the development of the parasite along with the arginase enzyme and synthesis of polyamides [37]. Studies in vitro have demonstrated that blocking the activity of receptor IL-10 may be a new effective treatment [38,39].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, different canine breeds present different prevalence rates [ 40 , 41 ]. Genes related to the activation of Th1 pathways include IL12RB1, JAK3 , CCRL2 , CCR2 , CCR3 , and CXCR6 , whereas COMMD5 and SHARPIN are associated with the activation of Th2 pathways [ 37 ]. Other genes, such as Slc11c11 or Major Histocompatibility Complex I gene ( MHCI ), also affect the susceptibility or resistance to L. infantum infection [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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Is the Prevalence of Leishmania infantum Linked to Breeds in Dogs? Characterization of Seropositive Dogs in Ibiza

Edo

Marín-Garcia

Llobat

2021

Animals

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Leishmaniosis is an important zoonotic protozoan disease primarily spread to the Mediterranean region by Leishmania infantum, the predominant protozoan species, which accounts for the majority of cases. Development of disease depends on the immune response of the definitive host and, predictably, their genetic background. Recent studies have revealed breed-typical haplotypes that are susceptible to the spread of the protozoan parasite. The objective of this study was to analyze the prevalence of leishmaniosis on a Mediterranean island and determine the relationship between disease prevalence and breed. In addition, information on seropositive animals was recorded to characterize animals affected by the disease. To study the prevalence, a total of 3141 dogs were analyzed. Of these, the 149 infected animals were examined for age, sex, antibody titer, and disease stage. We observed a prevalence of 4.74%, which varied between breeds (p < 0.05). The Doberman Pinscher and Boxer breeds had the highest prevalence of leishmaniosis. Significant differences were observed between breeds with common ancestors, emphasizing the important genetic component. Finally, regarding the characterization of seropositive animals, the distribution is similar to other studies. We discovered a relationship (p < 0.05) between the number of antibody titers and the clinical disease stage, which was also present in Leishmania infantum, suggesting that the development of the disease depends on the humoral or Th2 immune response with ineffective antibodies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Is the Prevalence of Leishmania infantum Linked to Breeds in Dogs? Characterization of Seropositive Dogs in Ibiza

Edo

Marín-Garcia

Llobat

2021

Animals

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“…For example, Lama2 -deficient mouse model shows elevated expression of proinflammatory cytokines, concretely, TNF-α and IL1β [ 53 ], and Li et al [ 57 ] demonstrated that LAMA2 is a coreceptor to activate T cells upon infection by S. aureus [ 54 ]. Thirteen intronic polymorphisms have been found in LTBP1 gene, a known gene involved in T regulatory lymphocyte differentiation [ 14 ]. In fact, Batista et al [ 14 ] performed a genome-wide association study of cell-mediate response in dogs infected by L. infantum , and their results showed several genetic markers, which explain the phenotypic variance in cytokines expression [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The allelic status of previously published polymorphisms and genomic regions described as related to the immune response to L. infantum infection in dogs [ 12 , 14 – 19 ] were interrogated in the analyzed samples.…”

Section: Methodsmentioning

confidence: 99%

Immunological and genomic characterization of Ibizan Hound dogs in an endemic Leishmania infantum region

2022

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Background The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniosis is an endemic zoonosis. Several studies indicate low prevalence of this disease in these dogs but the underlying molecular mechanism remains unknown. Methods In this study, qualitative immunological and genomic profiles of this breed have been analyzed. Results Our analysis shows relevant differences between the cytokine serum profile of Ibizan Hound dogs and previously published data from other canine strains. Additionally, several genetic risk variants related to the immune response, regulation of the immune system, and genes encoding cytokines and their receptors have been studied. The most relevant genes that presented such fixed polymorphisms were IFNG and IL6R. Other variants with frequencies ≥ 0.7 were found in the genes ARHGAP18, DAPK1, GNAI2, MITF, IL12RB1, LTBP1, SCL28A3, SCL35D2, PTPN22, CIITA, THEMIS, and CD180. Epigenetic regulatory genes such as HEY2 and L3MBTL3 showed also intronic polymorphisms. Conclusions Our analysis and results indicate that the regulation of immune responses is different in Ibizan Hounds compared to other breeds. Future studies are needed to elucidate whether these differences are related to the low prevalence of L. infantum infection in the Ibizan Hound. Graphical Abstract

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“…Efforts involving EMMAX include discovery of susceptibility loci for CanL [ 19 ], loci associated with canine cell-mediated response to L . infantum [ 22 ] and susceptibility human VL loci replicated in two independent samples [ 23 ]. In fact, the combination of an adjusted linear regression model with EMMAX restricted genomic inflation to acceptable levels even in a sub-structured multi-racial panel as observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Canine leishmaniasis: Genome-wide analysis and antibody response to Lutzomyia longipalpis saliva

et al. 2018

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The anti-inflammatory properties of sand fly saliva favor the establishment of the Leishmania infantum infection. In contrast, an antibody response against Lutzomyia longipalpis saliva is often associated with a protective cell-mediated response against canine visceral leishmaniasis. Genetic studies may demonstrate to what extent the ability to secrete anti-saliva antibodies depends on genetic or environmental factors. However, the genetic basis of canine antibody response against sand fly saliva has not been assessed. The aim of this study was to identify chromosomal regions associated with the anti-Lu. longipalpis salivary IgG response in 189 dogs resident in endemic areas in order to provide information for prophylactic strategies. Dogs were classified into five groups based on serological and parasitological diagnosis and clinical evaluation. Anti-salivary gland homogenate (SGH) IgG levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Genomic DNA was isolated from blood samples and genotyped using a SNP chip with 173,662 single nucleotide polymorphism (SNP) markers. The following linear regression model was fitted: IgG level = mean + origin + sex + age + use of a repellent collar, and the residuals were assumed as pseudo-phenotypes for the association test between phenotypes and genotypes (GWA). A component of variance model that takes into account polygenic and sample structure effects (EMMAX) was employed for GWA. Phenotypic findings indicated that anti-SGH IgG levels remained higher in exposed and subclinically infected dogs than in severely diseased dogs even in regression model residuals. Five associated markers were identified on chromosomes 2, 20 and 31. The mapped genes included CD180 (RP105) and MITF related to the rapid activation of B lymphocytes and differentiation into antibody-secreting plasma cells. The findings pointed to chromosomal segments useful for functional confirmation studies and a search for adjuvant molecules of the anti-saliva response.

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

Cited by 12 publications

References 58 publications

Is the Prevalence of Leishmania infantum Linked to Breeds in Dogs? Characterization of Seropositive Dogs in Ibiza

Is the Prevalence of Leishmania infantum Linked to Breeds in Dogs? Characterization of Seropositive Dogs in Ibiza

Immunological and genomic characterization of Ibizan Hound dogs in an endemic Leishmania infantum region

Canine leishmaniasis: Genome-wide analysis and antibody response to Lutzomyia longipalpis saliva

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