Noticeable immune dysregulation-and-suppression in parvovirus affected dogs

IF 1.4 3区 农林科学 Q4 IMMUNOLOGY
Milad Shahbazi Asil , Niloofar Zarifian , Amirhossein Valafar , Darioush Shirani , Jalil Mehrzad
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Abstract

Canine parvovirus type 2 (CPV-2) is one of the most common causes of infectious diarrhea in small animals, with high mortality and morbidity. Information on the specific treatment option(s) for CPV diseases (CPVD) is unachievably little. So, the treatment is mainly supportive one. Disruption of dog's innate immune system in viral diseases simply occurs; presumably, the CPV-2 may change the level of some TLRs, interleukins, CD4 and CD8 in the leukocytes of CPVD dogs, and disruptive activities of these immune molecules might be attributable to severe CPVD in dogs. Study on the role of the key immune molecules in CPVD is rare. Herein, by conducting and relating the clinical, para-clinical, immunological and molecular diagnostic tests, we tried to establish how some key immune molecules behave in blood of parvovirus affected dogs. As such, in the 1st study, the mRNA levels of TLR2, TLR4, TLR9, IL-1β, IL-6, CD4 and CD8 genes in the leukocytes of CPVD were assessed with quantitative (q)RT-PCR along with CPV-2 detection by rapid immunochromatography and PCR tests. In a 2nd study, the same measurements as in the 1st study were evaluated in two groups of mild versus severe clinical signs of CPVD. Both in the 1st and the 2nd studies leukopenia, much more pronounced in the severe CPVD, and immune dysregulation were observed. In the 1st study, a noticeable increase in the mRNA levels of TLR2 and TLR4 was detected with a slight decrease in TLR9 and a significant decrease in the expression of IL-1β, IL-6, CD4 and CD8 in leukocytes of CPV-infected dogs. Compared to the mild CPVD, the intense of downregulating effects on those immune molecules in the 2nd study was remarkably much more pronounced in the severe CPVD. Overall, it proves strong immune dysregulation and suppression/incompetence and potential T-cells exhaustion in severely CPV-2-affected dogs. Technically and clinically, this would be substantially applicable in canine medicine. By targeting those key immune molecules and their signaling pathways, new clinicodiagnostic approaches for CPVD can be evolved, and biotechnicoclinically this would be substantially applicable in all physiopathological conditions of dogs.

Abstract Image

受细小病毒影响的狗出现明显的免疫失调和抑制。
犬细小病毒2型(CPV-2)是小动物感染性腹泻最常见的原因之一,死亡率和发病率很高。关于CPV疾病(CPVD)的具体治疗方案的信息少得可怜。因此,治疗主要是支持性的。病毒性疾病只会破坏狗的先天免疫系统;据推测,CPV-2可能会改变CPVD犬白细胞中一些TLR、白细胞介素、CD4和CD8的水平,这些免疫分子的破坏性活性可能归因于犬的严重CPVD。关于关键免疫分子在CPVD中的作用的研究很少。在此,通过进行和关联临床、准临床、免疫学和分子诊断测试,我们试图确定受细小病毒影响的狗的血液中一些关键免疫分子的行为。因此,在第一项研究中,通过定量(q)RT-PCR以及通过快速免疫层析和PCR检测CPV-2来评估CPVD白细胞中TLR2、TLR4、TLR9、IL-1β、IL-6、CD4和CD8基因的mRNA水平。在第二项研究中,对CPVD的轻度和重度临床症状的两组患者进行了与第一项研究相同的测量。在第一项和第二项研究中都观察到了白细胞减少症,在严重的CPVD中更为明显,以及免疫失调。在第一项研究中,在CPV感染的狗的白细胞中,TLR2和TLR4的mRNA水平显著增加,TLR9略有下降,IL-1β、IL-6、CD4和CD8的表达显著下降。与轻度CPVD相比,在第二项研究中,对这些免疫分子的强烈下调作用在重度CPVD中明显更为明显。总的来说,在严重受CPV-2影响的狗中,它证明了强大的免疫失调和抑制/无能以及潜在的T细胞耗竭。从技术和临床上讲,这将在犬类医学中基本适用。通过靶向这些关键免疫分子及其信号通路,可以进化出新的CPVD临床诊断方法,生物技术临床上这将基本适用于狗的所有生理病理条件。
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来源期刊
CiteScore
3.40
自引率
5.60%
发文量
79
审稿时长
70 days
期刊介绍: The journal reports basic, comparative and clinical immunology as they pertain to the animal species designated here: livestock, poultry, and fish species that are major food animals and companion animals such as cats, dogs, horses and camels, and wildlife species that act as reservoirs for food, companion or human infectious diseases, or as models for human disease. Rodent models of infectious diseases that are of importance in the animal species indicated above,when the disease requires a level of containment that is not readily available for larger animal experimentation (ABSL3), will be considered. Papers on rabbits, lizards, guinea pigs, badgers, armadillos, elephants, antelope, and buffalo will be reviewed if the research advances our fundamental understanding of immunology, or if they act as a reservoir of infectious disease for the primary animal species designated above, or for humans. Manuscripts employing other species will be reviewed if justified as fitting into the categories above. The following topics are appropriate: biology of cells and mechanisms of the immune system, immunochemistry, immunodeficiencies, immunodiagnosis, immunogenetics, immunopathology, immunology of infectious disease and tumors, immunoprophylaxis including vaccine development and delivery, immunological aspects of pregnancy including passive immunity, autoimmuity, neuroimmunology, and transplanatation immunology. Manuscripts that describe new genes and development of tools such as monoclonal antibodies are also of interest when part of a larger biological study. Studies employing extracts or constituents (plant extracts, feed additives or microbiome) must be sufficiently defined to be reproduced in other laboratories and also provide evidence for possible mechanisms and not simply show an effect on the immune system.
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