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1.
Emerg Microbes Infect ; 10(1): 1669-1674, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34374631

RESUMO

To provide more complete data on SARS-CoV-2 infections in dogs and cats in the U.S., we conducted a serosurvey on convenience serum samples from dogs (n=1336) and cats (n=956) collected from 48 states of the USA in 2020. An ELISA targeting the antibody against nucleocapsid identified eleven positive and two doubtful samples in cats, and five positive and five doubtful samples in dogs. A surrogate neutralization assay detecting antibodies blocking the attachment of the spike protein to ACE2 was positive with three of the ELISA positive and doubtful samples, and one of 463 randomly selected ELISA negative samples. These four positive samples were confirmed by SARS-CoV-2 virus neutralization testing. All were from cats, in New York, Florida, and New Jersey (n=2). The serosurvey results, one of the largest yet completed on dogs and cats globally, support the OIE and CDC positions that currently there is no evidence that pets play a role in the spread of SARS CoV-2 in humans.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/veterinária , Doenças do Gato/epidemiologia , Doenças do Gato/imunologia , Doenças do Cão/epidemiologia , Doenças do Cão/imunologia , SARS-CoV-2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Doenças do Gato/virologia , Gatos , Doenças do Cão/virologia , Cães , Ensaio de Imunoadsorção Enzimática , Humanos , Testes de Neutralização , Vigilância em Saúde Pública , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia
2.
Viruses ; 13(5)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069453

RESUMO

Understanding the ecological and epidemiological roles of pets in the transmission of SARS-CoV-2 is critical for animal and human health, identifying household reservoirs, and predicting the potential enzootic maintenance of the virus. We conducted a longitudinal household transmission study of 76 dogs and cats living with at least one SARS-CoV-2-infected human in Texas and found that 17 pets from 25.6% of 39 households met the national case definition for SARS-CoV-2 infections in animals. This includes three out of seventeen (17.6%) cats and one out of fifty-nine (1.7%) dogs that were positive by RT-PCR and sequencing, with the virus successfully isolated from the respiratory swabs of one cat and one dog. Whole-genome sequences of SARS-CoV-2 obtained from all four PCR-positive animals were unique variants grouping with genomes circulating among people with COVID-19 in Texas. Re-sampling showed persistence of viral RNA for at least 25 d-post initial test. Additionally, seven out of sixteen (43.8%) cats and seven out of fifty-nine (11.9%) dogs harbored SARS-CoV-2 neutralizing antibodies upon initial sampling, with relatively stable or increasing titers over the 2-3 months of follow-up and no evidence of seroreversion. The majority (82.4%) of infected pets were asymptomatic. 'Reverse zoonotic' transmission of SARS-CoV-2 from infected people to animals may occur more frequently than recognized.


Assuntos
COVID-19/epidemiologia , COVID-19/veterinária , Animais de Estimação/virologia , Animais , Anticorpos Neutralizantes/imunologia , Doenças do Gato/epidemiologia , Doenças do Gato/imunologia , Doenças do Gato/virologia , Gatos/virologia , Doenças do Cão/epidemiologia , Doenças do Cão/imunologia , Doenças do Cão/virologia , Cães/virologia , Humanos , Estudos Longitudinais , Animais de Estimação/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Texas/epidemiologia
3.
Viruses ; 13(4)2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917632

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.


Assuntos
Modelos Animais de Doenças , Phlebovirus/imunologia , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Vacinas Virais/imunologia , Animais , Doenças do Gato/imunologia , Doenças do Gato/prevenção & controle , Doenças do Gato/virologia , Gatos , Cricetinae , Doenças do Cão/imunologia , Doenças do Cão/prevenção & controle , Doenças do Cão/virologia , Cães , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Phlebovirus/patogenicidade , Primatas , Febre Grave com Síndrome de Trombocitopenia/imunologia
4.
Acta Trop ; 219: 105931, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33901440

RESUMO

Ehrlichia spp. are important tick-borne pathogens of animals in Brazil, and Ehrlichia canis is the most prevalent species infecting dogs. Moreover, Ehrlichia minasensis has also recently been identified as a novel ehrlichial agent that infects cattle in Brazil. The objective of this study was to determine whether dogs could be infected by E. minasensis. To investigate this possibility, sera (n = 429) collected from dogs in the Pantanal region were retrospectively analyzed for the presence of antibodies against E. canis and E. minasensis. Canine sera were screened by two isolates of E. canis in indirect immunofluorescence assay (IFA) and the majority (n = 298; 69.4%) had antibodies with endpoint titers ranging from 80 to 327,680. In order to further confirm E. canis-specific antibodies, IFA positive sera were analyzed by ELISA using E. canis-specific peptides (i.e. TRP19 and TRP36 US/BR/CR), which detected E. canis antibodies in 80.2% (239/298) of the dog sera. Fifty-nine (13.7%) samples had detectable antibodies to E. canis by IFA but were negative by E. canis peptide ELISA. These sera were then tested by E. minasensis IFA (Cuiaba strain) as antigen and 67.8% (40/59) were positive (titers ranging from 80 to 20,480). Eleven sera had antibody titers against E. minasensis at least two-fold higher than observed for E. canis and suggests that these dogs were previously infected with E. minasensis. The results of the present study suggest that multiple ehrlichial agents infect dogs in Brazil, which highlights the need to consider different Ehrlichia spp. in Brazilian dogs, particularly in areas where dogs are frequently exposed to multiple tick species. This investigation is the first to provide serologic evidence of E. minasensis infection in dogs from Brazil.


Assuntos
Doenças do Cão/diagnóstico , Ehrlichia/fisiologia , Ehrlichiose/veterinária , Testes Sorológicos , Animais , Anticorpos Antibacterianos/sangue , Bovinos , Doenças do Cão/imunologia , Cães , Ehrlichia/imunologia , Ehrlichiose/diagnóstico , Ehrlichiose/imunologia
5.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808256

RESUMO

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.


Assuntos
Sarcoma Histiocítico/metabolismo , Neoplasias/metabolismo , Terapia Viral Oncolítica/métodos , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Cinomose/metabolismo , Cinomose/virologia , Vírus da Cinomose Canina/patogenicidade , Doenças do Cão/imunologia , Cães , Feminino , Xenoenxertos , Sarcoma Histiocítico/veterinária , Sarcoma Histiocítico/virologia , Metaloendopeptidases/metabolismo , Camundongos , Camundongos SCID , Necrose/metabolismo , Neoplasias/virologia , Neovascularização Patológica/metabolismo , Vírus Oncolíticos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Microambiente Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Vet Surg ; 50(5): 1032-1041, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33769592

RESUMO

OBJECTIVE: To investigate histopathological features of synovium from dogs with cranial cruciate ligament disease (CCLD) to seek mechanisms of osteoarthritis (OA) associated with CCLD. STUDY DESIGN: Retrospective, single-institution case series. ANIMALS: Thirty client-owned dogs. METHODS: Synovial biopsies (n = 30) obtained from stifles with CCLD were assessed by using two synovitis histopathology grading systems (Krenn and Hospital for Special Surgery [HSS]). The Krenn synovitis score was interpreted as "no synovitis," "low-grade," or "high-grade," while inflammatory subtype (low, mixed, or high) was determined by a computational algorithm within the HSS system. Comparison of synovitis scores was based on degree of CCL rupture and presence of meniscal tears. RESULTS: Histopathological changes and synovitis scores were similar regardless of degree of rupture (partial n = 5, complete n = 25) or presence of meniscal injury (n = 12) and were characterized by hyperplastic and lymphoplasmacytic synovitis with increased vascularity (30/30) and the presence of hemosiderin deposits (28/30), binucleated plasma cells (28/30), mucoid change (25/30), and Mott cells (16/30). Thirteen (43%) specimens were consistent with high-grade synovitis according to the Krenn system, while 11 (37%) specimens fit into the high-inflammatory subtype with the HSS system. CONCLUSION: Synovitis associated with canine CCLD in this study population was lymphoplasmacytic and was often highly inflammatory, with the presence of cells pertaining to humoral immunity. Humoral immune responses may play key roles in the synovitis associated with CCLD. CLINICAL SIGNIFICANCE: Modulation of biological factors that provoke humoral immune responses may mitigate symptoms of OA that persist and progress even after surgical treatment of CCLD in dogs.


Assuntos
Ligamento Cruzado Anterior/imunologia , Doenças do Tecido Conjuntivo/veterinária , Doenças do Cão/imunologia , Imunidade Humoral/imunologia , Membrana Sinovial/patologia , Sinovite/veterinária , Animais , Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/veterinária , Doenças do Tecido Conjuntivo/imunologia , Doenças do Cão/patologia , Cães , Feminino , Masculino , Osteoartrite/veterinária , Estudos Retrospectivos , Ruptura Espontânea/veterinária , Joelho de Quadrúpedes/cirurgia , Sinovite/imunologia , Sinovite/patologia
7.
Vet J ; 270: 105611, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33641807

RESUMO

This two-part article discusses the mechanisms by which genetic variation can influence the risk of complex diseases, with a focus on canine diabetes mellitus. In Part 1, presented here, the importance of accurate methods for classifying different types of diabetes will be discussed, since this underpins the selection of cases and controls for genetic studies. Part 2 will focus on our current understanding of the genes involved in diabetes risk, and the way in which new genome sequencing technologies are poised to reveal new diabetes genes in veterinary species.


Assuntos
Diabetes Mellitus/veterinária , Doenças do Cão/genética , Predisposição Genética para Doença , Fenótipo , Animais , Diabetes Mellitus/classificação , Diabetes Mellitus/genética , Doenças do Cão/imunologia , Cães , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Humanos , Resistência à Insulina , Células Secretoras de Insulina/imunologia , Obesidade/veterinária , Especificidade da Espécie
8.
Vet J ; 270: 105612, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33641811

RESUMO

Part 1 of this 2-part review outlined the importance of disease classification in diabetes genetic studies, as well as the ways in which genetic variants may contribute to risk of a complex disease within an individual, or within a particular group of individuals. Part 2, presented here, describes in more detail our current understanding of the genetics of canine diabetes mellitus compared to our knowledge of the human disease. Ongoing work to improve our knowledge, using new technologies, is also introduced.


Assuntos
Diabetes Mellitus/veterinária , Doenças do Cão/genética , Predisposição Genética para Doença/genética , Animais , Diabetes Mellitus/classificação , Diabetes Mellitus/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Doenças do Cão/classificação , Doenças do Cão/imunologia , Cães , Antígenos HLA/genética , Antígenos HLA/imunologia , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Humanos , Imunidade/genética , Células Secretoras de Insulina/imunologia , Complexo Principal de Histocompatibilidade/genética , Mutação
9.
Vet Parasitol ; 291: 109366, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33545559

RESUMO

The common signs of canine babesiosis caused by an infection with Babesia canis are fever, anorexia, lethargy, pulse alterations, anemia, and occasionally mild icterus. Dogs with these clinical signs can be divided into two groups: those with acute-phase reaction and those with systemic inflammatory response syndrome (SIRS). Factors associated with the occurrence of SIRS in canine babesiosis have not been thoroughly researched. This article outlines a cross-sectional study of 54 client-owned dogs with an acute B. canis infection, and evaluates the differences in age, gender, laboratory findings, parasite load, and seroreactivity against B. canis between the SIRS and the SIRS-free dogs. We have analyzed a complete blood count, serum biochemistry, serum amyloid A, ceruloplasmin, paraoxonase-1, serology, and PCR testing using standard methodologies. The frequency of SIRS among the investigated dogs reached 0.59. Male dogs and those seronegative against B. canis, were more frequent in the SIRS group, whilst age and parasite load could not be associated with the presence of SIRS. Dogs with SIRS had a lower count of total leukocytes, neutrophils, lymphocytes, and monocytes, and a lower concentration of iron and bilirubin compared with SIRS-free dogs. No significant differences in the concentration of acute-phase proteins have been noticed to exist between the groups of dogs. Further, the seronegative dogs had a lower count of lymphocytes and monocytes and a higher parasite load than the seroreactive dogs. Multivariate logistic regression analysis has identified leukopenia (<6 × 109/L) and monocytopenia (<0.2 × 109/L) as independent associates of SIRS in the investigated dogs, thus implying that these routine tests could be used as reliable markers for SIRS.


Assuntos
Babesiose/complicações , Doenças do Cão/imunologia , Interações Hospedeiro-Parasita/imunologia , Carga Parasitária/veterinária , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Animais , Babesia , Babesiose/imunologia , Babesiose/parasitologia , Biomarcadores/sangue , Doenças do Cão/parasitologia , Cães , Feminino , Masculino , Síndrome de Resposta Inflamatória Sistêmica/parasitologia
10.
Vet Microbiol ; 254: 108997, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33524810

RESUMO

Canine influenza (CI) is a contagious respiratory disease in dogs, which poses a threat to canine health. A safe, high-yield vaccine seed virus is critical for CI vaccine development. We developed a PR8-based reassortant H3N2 canine influenza virus (RT CIV) using the reverse genetic method and evaluated its yield in canine kidney epithelial (MDCK) cells, Vero cells, and specific pathogen-free (SPF) chicken embryos. Mice and dogs were infected with RT CIV, and the pathogenicity was evaluated. The viral titers of RT CIV increased in MDCK cells, Vero cells, and SPF chicken embryos; the HA yield in SPF chicken embryos increased 4-fold. However, RT CIV was not lethal to mice, and it showed similar virulence as wild-type CIV. RT CIV also showed minimal pathogenicity in dogs, which manifested as mild fever and rhinorrhea for the first two days post-infection. Thus, RT CIV carrying the internal gene cassette from PR8 showed almost no pathogenicity in dogs. And the reassortant virus inactivated vaccine could provide complete protection against H3N2 CIV. To our knowledge, this is the first report on the pathogenicity of PR8-based reassortant H3N2 CIV in dogs. These studies are relevant for developing a high-yield and safe CI vaccine.


Assuntos
Doenças do Cão/prevenção & controle , Doenças do Cão/virologia , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/genética , Animais , Anticorpos Antivirais/sangue , Chlorocebus aethiops , Doenças do Cão/imunologia , Cães , Feminino , Células HEK293 , Humanos , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Vírus Reordenados/patogenicidade , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Células Vero , Replicação Viral
11.
Viruses ; 13(2)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530411

RESUMO

(1) Background: Antibody testing is commonly used to assess a dog's immune status. For detection of antibodies against canine adenoviruses (CAVs), one point-of-care (POC) test is available. This study assessed the POC test´s performance. (2) Methods: Sera of 198 privately owned dogs and 40 specific pathogen-free (SPF) dogs were included. The reference standard for detection of anti-CAV antibodies was virus neutralization (VN) using CAV-1 and CAV-2 antigens. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy (OA) of the POC test were assessed. Specificity was considered most important. (3) Results: Prevalence of CAV-1 neutralizing antibodies (≥10) was 76% (182/238) in all dogs, 92% (182/198) in the subgroup of privately owned dogs, and 0% (0/40) in SPF dogs. Prevalence of CAV-2 neutralizing antibodies (≥10) was 76% (181/238) in all dogs, 91% (181/198) in privately owned dogs, and 0% (0/40) in SPF dogs. Specificity for detection of CAV-1 antibodies was lower (overall dogs, 88%; privately owned dogs, 56%; SPF dogs, 100%) compared with specificity for detection of CAV-2 antibodies (overall dogs, 90%; privately owned dogs, 65%; SPF dogs, 100%). (4) Conclusions: Since false positive results will lead to potentially unprotected dogs not being vaccinated, specificity should be improved to reliably detect anti-CAV antibodies that prevent infectious canine hepatitis in dogs.


Assuntos
Infecções por Adenoviridae/veterinária , Adenovirus Caninos/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Doenças do Cão/imunologia , Testes Imediatos , Infecções por Adenoviridae/imunologia , Vacinas contra Adenovirus , Animais , Cães , Ensaio de Imunoadsorção Enzimática , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Vacinação/veterinária
12.
BMC Vet Res ; 17(1): 71, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546688

RESUMO

BACKGROUND: In dogs with atopic dermatitis, intradermal testing (IDT) or allergen specific IgE serological testing are routinely employed to identify causative allergens. These allergens can then be used for allergen-specific immunotherapy and allergy management. The clinical relevance of this testing is affected by the source of allergen, and other biomarkers that are more related to specific allergens still need to be identified. The aim of this study was to investigate levels of specific IgE, total IgG, and IgG1 and IgG2 subclasses against the local house dust mites (HDM) Dermatophagoides farinae (DF) and D. pteronyssinus (DP) as biomarkers by using in-house ELISAs in healthy (n = 33) and atopic dogs (AD) (n = 44) that were either positive or negative by IDT to HDM. RESULTS: Being over 3 years of age was a risk factor for AD (Odds Ratio (OD) = 4.10, 95% Confidence interval (CI) 1.57-10.75, p = 0.0049), but there was no relation to IDT outcomes (OR = 0.9091, 95% CI 0.22-3.74, p = 1.00). High levels of all antibody isotypes (IgE, IgG, IgG1 and IgG2) against HDM were found in aged healthy dogs (> 3 years old). In AD, HDM-IgE and IgG1 levels were higher in dogs that were IDT positive to HDM than in IDT negative animals. Levels of IgE and IgG1 could be used to distinguish the specific allergens, whereas total IgG and IgG2 levels were not different between IDT-positive and IDT-negative AD. By the receiver operating characteristic curve at a false-positive rate = 0.10, both IgE and IgG1 showed better sensitivity than IgG and IgG2. Similar to IgE, serum IgG1 concentration was also relevant to IDT outcomes. CONCLUSIONS: Our in-house ELISAs coated with local HDM were useful for evaluating antibody levels, and we propose use of the HDM-specific IgG1 subclass as a biomarker to detect HDM specific allergens in AD, potentially together with an IgE based platform.


Assuntos
Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Doenças do Cão/imunologia , Imunoglobulina G/imunologia , Alérgenos/imunologia , Animais , Dermatite Atópica/imunologia , Dermatite Atópica/veterinária , Doenças do Cão/diagnóstico , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Imunoglobulina E/imunologia , Masculino , Testes Cutâneos/veterinária
13.
Res Vet Sci ; 136: 32-38, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33582312

RESUMO

Among the innate and adaptative immune cells recruited to the tumour site, tumour associated macrophages (TAMs) are particularly abundant and by simplified classification can be classified into (M1) and (M2) TAMs. In the present study, we quantified by immunohistochemistry ionized calcium binding adaptor molecule 1 (Iba1)-positive total and CD204-positive M2-polarized TAMs in 60 canine malignant mammary tumours (CMMTs) to analyze the relationship between M1 or M2 response and the histopathologic features of examined CMMTs, the dogs' body condition score (BCS) and the progression of the neoplastic disease. The mean number of total and CD204+ TAMS were significantly higher in solid and in grade III than in grades I and II carcinomas. Moreover, the mean number of CD204-positive TAMs was significantly higher in CMMTs with lymphatic invasion and necrosis rather than CMMTs without. The presence of higher number of CD204-positive M2-polarized TAMs was associated with a worst outcome of the neoplastic disease: bitches bearing CMMTs with a prevalent M2-polarized TAM response had a median cancer-specific survival time of 449 days, while in animals with a M1-polarized TAM response the median cancer-specific survival time was 1209 days. The results of our study confirm that in CMMTs the presence of a M2-polarized TAMs response might affect the tumour development and behaviour. Finally, it strongly suggests the potential of CD204 expression as a prognostic factor.


Assuntos
Doenças do Cão/imunologia , Neoplasias Mamárias Animais/imunologia , Macrófagos Associados a Tumor/imunologia , Animais , Cães , Feminino , Imuno-Histoquímica , Neoplasias Mamárias Animais/classificação , Prognóstico
14.
PLoS Negl Trop Dis ; 15(2): e0009137, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33617528

RESUMO

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.


Assuntos
Suscetibilidade a Doenças/veterinária , Doenças do Cão/parasitologia , Leishmaniose Visceral/veterinária , Psychodidae , Animais , Mordeduras e Picadas/veterinária , Brasil , Dinoprostona/sangue , Suscetibilidade a Doenças/parasitologia , Doenças do Cão/imunologia , Cães , Feminino , Insetos Vetores , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/transmissão , Masculino , Carga Parasitária/veterinária , Estudos Prospectivos , Saliva/imunologia , Baço/parasitologia
15.
Vet Immunol Immunopathol ; 233: 110198, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548792

RESUMO

Visceral leishmaniasis (VL) is an important zoonotic vector-borne disease and domestic dogs are considered the main domiciliary and peri-domiciliary reservoir of Leishmania (Leishmania) infantum in South America. Distinct eco-epidemiological scenarios associated to the prevalence of the disease, clusters of parasite genotypes and chemotypes of vectors population are described in Brazil, especially in the state of São Paulo (SP). In this context, the purpose of the present study is to evaluate the clinical signs, histopathological lesions, parasite load and cytokine profile by immunohistochemistry (IHC) in popliteal lymph nodes of canines naturally infected with L. infantum, from different municipalities of the state of SP. Eighty-three dogs with VL, 61 from northwest SP (NWSP) and 22 from southeast SP (SESP), were clinically classified in stage II, with no babesiosis and ehrlichiosis. Subcapsular inflammatory infiltration and histiocytosis were significantly higher in the SESP group (p = 0.0128; 0.0077, respectively). On the other hand, dogs from NWSP revealed 4.6-fold significantly higher parasite burden (p = 0.0004) and higher IHC scores of IL-1ß (p = 0.0275) and IL-4 (p = 0.0327) in the popliteal lymph node tissues, which may be associated with the susceptibility and progression of the disease in these dogs. Differences in immune response profile associated with higher parasite load in dogs can also contribute to explain the distinct eco-epidemiological patterns of VL in specific geographic regions.


Assuntos
Citocinas/imunologia , Doenças do Cão/imunologia , Leishmania infantum , Leishmaniose Visceral/veterinária , Linfonodos/parasitologia , Animais , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Doenças do Cão/patologia , Cães , Feminino , Leishmania infantum/imunologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Linfonodos/patologia , Masculino , Carga Parasitária
16.
Vet Immunol Immunopathol ; 232: 110169, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387703

RESUMO

BACKGROUND: Immune-targeted therapies are being successfully implemented into cancer clinical practice. In particular checkpoint inhibitors are employed to modulate the immune microenvironment of solid tumors. We sought to determine the expression of PD-L1, HVEM, and B7H3 in human and canine osteosarcoma, and correlate expression with clinical features and tumor infiltrating lymphocytes in naturally-occurring canine osteosarcoma. METHODS: Flow cytometry was used to measure ligand surface expression of five human and three canine cell lines. Immunohistochemistry was utilized for expression of ligands and lymphocyte markers in thirty-seven treatment-naïve canine osteosarcoma patients. RESULTS: All cell lines expressed all three ligands at variable levels in both species. Metastatic lesions were associated with higher expression of all three ligands in patient tumor samples. PD-L1 expression strongly correlated with B7H3 and HVEM expression, while HVEM and B7H3 were weakly correlated. Whereas peritumoral T-cell expression positively correlated with PD-L1 and HVEM tumor expression, the presence of T-cells intratumorally were rare. Furthermore, intratumor penetration by T-cells was greatest in metastatic lesions, despite log-fold increases in peritumoral T-cells. In summary, PD-L1, HVEM, and B7H3 are expressed in osteosarcoma, with metastatic disease lesions expressing higher levels. We show for the first time that these ligands expressed on osteosarcoma cells positively correlate with each other and the presence of peritumoral T cell infiltration. Furthermore, osteosarcoma appears to be an intratumoral immune desert with significant resistance to effector T cells. Multiple agents targeting checkpoints are in clinical practice, and may have immune modulating benefit in osteosarcoma.


Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/imunologia , Linfócitos do Interstício Tumoral/imunologia , Osteossarcoma/veterinária , Linfócitos T/imunologia , Animais , Antígenos de Neoplasias/biossíntese , Antígenos B7/biossíntese , Antígeno B7-H1/biossíntese , Western Blotting/veterinária , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/secundário , Linhagem Celular , Cães , Feminino , Citometria de Fluxo , Humanos , Masculino , Osteossarcoma/imunologia , Osteossarcoma/secundário , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Membro 14 de Receptores do Fator de Necrose Tumoral/biossíntese
17.
Res Vet Sci ; 135: 442-449, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33187678

RESUMO

Canine degenerative myelopathy (DM) is an adult-onset fatal disease characterized by progressive degeneration of the spinal cord. Affected dogs have homozygous mutations in superoxide dismutase 1, and thus DM is a potential spontaneous animal model of human familial amyotrophic lateral sclerosis (ALS). Neuroinflammation is the pathological hallmark of ALS, whereby proinflammatory cytokines and chemokines are overproduced by activated glial cells such as astrocytes and microglia. However, the detailed pathogenesis of spinal cord degeneration in DM remains unknown. To further characterize the pathological mechanism of DM, we analyzed the caudal cervical cords of ten Pembroke Welsh Corgis pathologically diagnosed with DM by quantitative real-time reverse transcription polymerase chain reaction, immunohistochemistry (IHC), and double immunofluorescence. Compared to control spinal cord tissues, we found significantly enhanced transcriptions of interleukin-1ß, tumor necrosis factor-α, CC motif chemokine ligand (CCL) 2 and vascular cell adhesion molecule -1 mRNA in the spinal cords of DM dogs. Moreover, IHC for the class II major histocompatibility complex molecules HLA-DR and CCL2 indicated that the immunopositive areas of activated macrophages/microglia and CCL2 protein were significantly increased in DM, and CCL2 protein was mainly overproduced by astrocytes. Our results suggest a proinflammatory state of the microenvironment in the DM spinal cord in which activated microglia and astrocytes play important roles by secreting a set of cytokines, chemokines, and expressing adhesion molecules.


Assuntos
Doenças do Cão/metabolismo , Mediadores da Inflamação/metabolismo , Doenças da Medula Espinal/veterinária , Animais , Doenças do Cão/imunologia , Cães , Feminino , Imuno-Histoquímica/veterinária , Ativação de Macrófagos , Macrófagos/metabolismo , Masculino , Mutação , Medula Espinal/patologia , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/metabolismo , Doenças da Medula Espinal/patologia , Superóxido Dismutase-1/genética , Regulação para Cima
18.
Res Vet Sci ; 135: 329-334, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33097278

RESUMO

Tumor-associated macrophages (TAMs) have been involved in growth and metastases of human and canine mammary tumors. However, the prognostic importance of TAM specific location in canine mammary tumors (CMT) was not evaluated. In this study, we evaluated the potential role of TAMs in specific histologic locations - intratumoral (iTAM) and stromal (sTAM), as well as total macrophage (tTAM) counts - as prognostic indicators in CMT. Clinicopathologic data from 66 animals with mammary carcinoma and their tumors were used in this study. Samples were stained with anti-macrophage antibody for subsequent TAM count. High levels of iTAM, sTAM, and tTAM were related with advanced clinical stage and vascular invasion. Additionally, tTAM revealed a relation with larger tumor size, while high levels of sTAM and tTAM were also correlated with node metastasis and a poor prognosis based on survival analysis. CMT with aggressive features can reveal higher TAM counts. TAMs are associated with vascular invasion and nodal metastasis, and sTAM and tTAM counts are correlated with overall survival, suggesting they could be used as prognostic indicators in canine mammary carcinomas.


Assuntos
Doenças do Cão/imunologia , Neoplasias Mamárias Animais/imunologia , Macrófagos Associados a Tumor/imunologia , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Feminino , Neoplasias Mamárias Animais/diagnóstico , Neoplasias Mamárias Animais/patologia , Prognóstico
19.
Res Vet Sci ; 134: 58-63, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33302213

RESUMO

Visceral Leishmaniasis (VL) is a neglected tropical disease, caused by L. infantum in the New World, where dogs are the main reservoir. These parasites can regulate host immune response through miRNA differential expression in the early stages of infection; however such early response has not yet been investigated in the canine model. PBMC from healthy dogs were exposed to L. infantum in vitro and microarray analysis showed an upregulation of miR-206, miR-302d, miR-433, miR-214, miR-493, miR-514, miR-1835, miR-210, miR-539, miR-432, miR-188, miR-345 and downregulation of miR-489 and miR-503 in comparison to non-exposed control cells, at 24 h post-exposure. In silico target prediction showed that the upregulated miRNAs target 1541 genes, which can modulate important pathways involved in the early immune responses, like the "MAPK signaling pathway", one of the most relevant pathways to Leishmania survival inside host cells. These findings shed light on parasite modulation of host immunity following Leishmania infection, which in turn can be explored for drug development.


Assuntos
Doenças do Cão/parasitologia , Leishmania infantum , Leishmaniose Visceral/veterinária , Leucócitos Mononucleares/metabolismo , MicroRNAs/metabolismo , Animais , Células Cultivadas , Doenças do Cão/sangue , Doenças do Cão/genética , Doenças do Cão/imunologia , Cães , Regulação para Baixo , Leishmaniose Visceral/sangue , Leishmaniose Visceral/genética , Leishmaniose Visceral/imunologia , Sistema de Sinalização das MAP Quinases
20.
Vet J ; 267: 105581, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33375962

RESUMO

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG. No alteration in frequency of either MDSCs or Tregs in dogs with MG was observed when compared to those in either seronegative dogs with diagnoses other than MG, or healthy dogs. A longitudinal study in three dogs with MG revealed no correlation between the relative numbers of either population and the clinical course of disease. Neither the frequency of MDSCs nor of Tregs showed a correlation with anti-AChR antibody titer in dogs with MG. These findings suggest that aberrations in the frequency of either immunosuppressive population do not occur in MG, but they need to be validated in large-scale prospective studies.


Assuntos
Doenças do Cão/imunologia , Miastenia Gravis/veterinária , Células Supressoras Mieloides/imunologia , Projetos Piloto , Linfócitos T Reguladores/imunologia , Animais , Contagem de Células , Cães , Estudos Longitudinais , Miastenia Gravis/sangue , Miastenia Gravis/imunologia
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