Altered apoptosis and proliferation in milk cells and PBMc from BLV-infected bovines with different proviral loads: Possible role of the BCL-2 family proteins, TNF-alpha, and receptors

IF 1.4 3区 农林科学 Q4 IMMUNOLOGY
M.E. Ladera Gómez , M.V. Nieto Farias , M. Rodríguez , A. Váter , M.C. Ceriani , G.L. Dolcini
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引用次数: 0

Abstract

Bovines infected by bovine leukemia virus (BLV) are characterized by presenting low proviral load (LPL) or high proviral load (HPL). It is reported that animals with HPL in peripheral blood mononuclear cells (PBMCs) present a decrease in apoptosis, an increase in viability and the proliferation rate, while animals that maintain an LPL have an intrinsic ability to control the infection, presenting an increased apoptosis rate of their PBMCs. However, there is little information on the effect of BLV on these mechanisms when the virus infects somatic milk cells (SC). This study investigates the mechanisms underlying apoptosis in milk and blood from BLV-infected animals with HPL and LPL. Relative levels of mRNA of tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNF-RI), TNF receptor 2 (TNF-RII), anti-apoptotic B-cell lymphoma 2 protein (Bcl-2), and pro-apoptotic Bcl-2-like protein 4 (Bax) were measured in SC and PBMCs using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. A significant decrease in the expression of TNF-α in SC from HPL animals vs non-infected bovines was observed, but the infection in SC with BLV did not show a modulation on the expression of TNF receptors. A significant increase in TNF-RI expression in PBMCs from HPL bovines compared to LPL bovines was observed. No significant differences in PBMCs between HPL and LPL compared to non-infected animals concerning TNF-α, TNF-RI, and TNF-RII expression were found. There was a significant increase of both Bcl-2 and Bax in SC from LPL compared to non-infected bovines, but the Bcl-2/Bax ratio showed an anti-apoptotic profile in LPL and HPL bovines compared to non-infected ones. Reduced mRNA expression levels of Bax were determined in the PBMCs from HPL compared to LPL subjects. In contrast, BLV-infected bovines did not differ significantly in the mRNA expression of Bax compared to non-infected bovines. Our data suggest that the increased mRNA expression of Bax corresponds to the late lactation state of bovine evaluated and the exacerbated increase of mRNA expression of Bcl-2 may be one of the mechanisms for the negative apoptosis regulation in the mammary gland induced by BLV infection. These results provide new insights into the mechanism of mammary cell death in HPL and LPL BLV-infected bovine mammary gland cells during lactation.

不同病毒载量下受 blv 感染的牛的乳细胞和 pbmc 的凋亡和增殖发生变化:Bcl-2家族蛋白、TNF-α和受体的可能作用
感染牛白血病病毒(BLV)的牛的特征是呈现低病毒载量(LPL)或高病毒载量(HPL)。据报道,外周血单核细胞(PBMCs)中存在 HPL 的动物凋亡率下降,存活率和增殖率上升,而保持 LPL 的动物有内在控制感染的能力,其 PBMCs 的凋亡率上升。然而,关于 BLV 感染体乳细胞(SC)时对这些机制的影响的信息却很少。本研究调查了BLV感染HPL和LPL动物的乳汁和血液中细胞凋亡的机制。采用定量反转录聚合酶链反应(RT-qPCR)法测定了SC和PBMC中肿瘤坏死因子-α(TNF-α)、TNF受体1(TNF-RI)、TNF受体2(TNF-RII)、抗凋亡B细胞淋巴瘤2蛋白(Bcl-2)和促凋亡Bcl-2样蛋白4(Bax)的mRNA相对水平。与未感染的牛相比,观察到 HPL 动物的 SC 中 TNF-α 的表达明显下降,但感染 BLV 的 SC 并未显示出 TNF 受体的表达变化。与 LPL 牛相比,在 HPL 牛的 PBMCs 中观察到 TNF-RI 表达明显增加。与未感染的动物相比,HPL 和 LPL 的 PBMC 在 TNF-α、TNF-RI 和 TNF-RII 表达方面没有发现明显差异。与未感染的牛相比,LPL 牛的 SC 中 Bcl-2 和 Bax 均明显增加,但与未感染的牛相比,LPL 和 HPL 牛的 Bcl-2/Bax 比值显示出抗凋亡特征。与 LPL 受试者相比,HPL 受试者的 PBMCs 中 Bax 的 mRNA 表达水平降低。相比之下,BLV 感染的牛群与未感染的牛群相比,Bax 的 mRNA 表达量没有显著差异。我们的数据表明,Bax mRNA表达的增加与牛的泌乳后期状态相对应,而Bcl-2 mRNA表达的加剧增加可能是BLV感染诱导乳腺凋亡负调控的机制之一。这些结果为了解泌乳期受 HPL 和 LPL BLV 感染的牛乳腺细胞死亡机制提供了新的视角。
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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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