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Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections. 三维模型的宫颈阴道上皮研究宿主-微生物相互作用和性传播感染。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-08-27 DOI: 10.1093/femspd/ftac026
Vonetta L Edwards, Elias McComb, Jason P Gleghorn, Larry Forney, Patrik M Bavoil, Jacques Ravel

2D cell culture systems have historically provided controlled, reproducible means to analyze host-pathogen interactions observed in the human reproductive tract. Although inexpensive, straightforward, and requiring a very short time commitment, these models recapitulate neither the functionality of multilayered cell types nor the associated microbiome that occurs in a human. Animal models have commonly been used to recreate the complexity of human infections. However, extensive modifications of animal models are required to recreate interactions that resemble those in the human reproductive tract. 3D cell culture models have emerged as alternative means of reproducing vital elements of human infections at a fraction of the cost of animal models and on a scale that allows for replicative experiments. Here, we describe a new 3D model that utilizes transwells with epithelial cells seeded apically and a basolateral extracellular matrix (ECM)-like layer. The model produced tissues with morphologic and physiological resemblance to human cervical and vaginal epithelia, including mucus levels produced by cervical cells. Infection by Chlamydia trachomatis and Neisseria gonorrhoeae was demonstrated, as well as the growth of bacterial species observed in the human vaginal microbiota. This enabled controlled mechanistic analyses of the interactions between host cells, the vaginal microbiota, and STI pathogens. Affordable and semi high-throughput 3D models of the cervicovaginal epithelia that are physiologically relevant by sustaining vaginal bacterial colonization, and facilitate studies of chlamydial and gonococcal infections.

二维细胞培养系统历来为分析人类生殖道中观察到的宿主-病原体相互作用提供了可控的、可重复的手段。尽管这些模型便宜、简单,而且需要很短的时间投入,但它们既没有概括出多层细胞类型的功能,也没有概括出人体中出现的相关微生物组。动物模型通常被用来重现人类感染的复杂性。然而,需要对动物模型进行广泛的修改,以重建类似于人类生殖道的相互作用。3D细胞培养模型已经成为复制人类感染的重要因素的替代手段,其成本仅为动物模型的一小部分,并且可以进行复制实验。在这里,我们描述了一种新的3D模型,该模型利用带有顶部上皮细胞和基底外侧细胞外基质(ECM)样层的transwell。该模型产生的组织在形态和生理上与人宫颈和阴道上皮相似,包括宫颈细胞产生的粘液水平。证实了沙眼衣原体和淋病奈瑟菌的感染,以及在人类阴道微生物群中观察到的细菌种类的生长。这使得宿主细胞、阴道微生物群和性传播感染病原体之间相互作用的控制机制分析成为可能。可负担和半高通量的宫颈阴道上皮3D模型,与维持阴道细菌定植的生理相关,并促进衣原体和淋球菌感染的研究。
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引用次数: 0
Examination of vertical transmission of Bartonella quintana in body lice following multiple infectious blood meals. 多次感染性血食后体虱垂直传播的检验。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-08-17 DOI: 10.1093/femspd/ftac028
Lauren Kress, Rashaun Potts, Jose E Pietri

Bartonella quintana is a re-emerging louse-borne pathogen. Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria. However, questions have remained about whether vertical transmission from infected vectors to their progeny, which could significantly influence the dynamics of transmission to humans, occurs in body lice. To address this subject, we performed a series of controlled laboratory experiments that examined the presence of B. quintana on the surface of and within eggs produced by female body lice that were provisioned multiple infectious blood meals to recapitulate the natural pathogen acquisition process. Our results demonstrate that B. quintana DNA can be detected from the surface of eggs by qPCR due to vertical transfer of infectious feces to the egg sheath during or after oviposition. However, viable B. quintana could not be cultured from the hemolymph of adult female lice or from within eggs that were surface sterilized, indicating a lack of true transovarial transmission. Based on this evidence, vertical transfer of B. quintana from infected adult lice to their eggs probably has a limited impact on the dynamics of transmission to humans.

金塔纳巴尔通体是一种重新出现的虱传病原体。从体虱媒介(人蒂虱)向人类宿主的水平传播是通过接触含有高浓度细菌的传染性虱子粪便发生的。然而,从受感染媒介到其后代的垂直传播是否会在体虱中发生,这一问题仍然存在,这可能会显著影响向人类传播的动态。为了解决这一问题,我们进行了一系列对照实验室实验,检查了在雌性体虱产生的卵表面和卵内是否存在黄芽孢杆菌,这些体虱被提供了多次感染性血餐,以重现自然病原体获取过程。我们的研究结果表明,由于感染粪便在产卵期间或产卵后垂直转移到卵鞘中,因此可以通过qPCR从卵表面检测到金黄色小蠊的DNA。然而,成年雌虱的血淋巴和表面绝育的卵中都无法培养出活的昆塔纳白僵菌,这表明它缺乏真正的经卵巢传播。根据这一证据,从受感染的成年虱子到它们的卵的垂直转移可能对人类传播的动态影响有限。
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引用次数: 1
Using champion-oriented mindset to overcome the challenges of graduate school: impact of workshop for graduate school skills on underrepresented minority retention. 用冠军导向的心态克服研究生院的挑战:研究生院技能研讨会对未被充分代表的少数民族保留的影响。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-08-13 DOI: 10.1093/femspd/ftac024
Andrea G Marshall, Caroline B Palavicino-Maggio, Kit Neikirk, Zer Vue, Heather K Beasley, Edgar Garza-Lopez, Sandra A Murray, Denise Martinez, Amber Crabtree, Zachary C Conley, Larry Vang, Jamaine S Davis, Keesha L Powell-Roach, Susan Campbell, Angyth B Dal, Bryanna Shao, Stefanie Alexander, Nancy Vang, Neng Vue, Mein Vue, Haysetta D Shuler, Elsie C Spencer, Derrick J Morton, Antentor Hinton

Despite efforts to increase diversity, a glaring underrepresentation of minorities (URM) persists in the fields of science, technology, engineering, and mathematics (STEM). Graduate school can be a stressful step in the STEM pipeline, especially for students previously unaware of the structure and challenges of postgraduate education. To promote successful minority participation in STEM and prepare prospective students for the impending challenges of applying for and attending graduate school, we developed a workshop based on the mentoring and fostering of a champion-oriented mindset entitled, "The Trials and Tribulations of Graduate School: How Do You Make an Impact?." Students from the HBCU Winston-Salem State University attended the workshop, and a pre/post-a 10-point Likert scale-based survey was administered. The questions used in this seminar were newly designed by the authors as program evaluations. The results suggest that the workshop was well-received by the students and provided information that they considered helpful to help navigate the graduate school process.

尽管努力增加多样性,但在科学、技术、工程和数学(STEM)领域,少数族裔(URM)的代表性明显不足。研究生院可能是STEM管道中压力很大的一步,特别是对于以前不了解研究生教育结构和挑战的学生。为了促进少数族裔成功参与STEM,并让未来的学生为即将到来的申请和就读研究生院的挑战做好准备,我们开发了一个基于指导和培养冠军导向心态的研讨会,题为“研究生院的考验和磨难:你如何产生影响?”来自HBCU温斯顿-塞勒姆州立大学的学生参加了研讨会,并进行了一项基于10分李克特量表的调查。本次研讨会使用的问题是作者新设计的程序评估问题。结果表明,研讨会受到了学生的好评,并提供了他们认为有助于导航研究生院过程的信息。
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引用次数: 1
The role of mentoring in promoting diversity equity and inclusion in STEM Education and Research. 指导在促进STEM教育和研究中的多样性公平和包容方面的作用。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-07-21 DOI: 10.1093/femspd/ftac019
Andrea G Marshall, Zer Vue, Caroline B Palavicino-Maggio, Kit Neikirk, Heather K Beasley, Edgar Garza-Lopez, Sandra A Murray, Denise Martinez, Amber Crabtree, Zachary C Conley, Larry Vang, Jamaine S Davis, Keesha L Powell-Roach, Susan Campbell, Lillian J Brady, Angyth B Dal, Bryanna Shao, Stefanie Alexander, Nancy Vang, Neng Vue, Mein Vue, Haysetta D Shuler, Elsie C Spencer, Derrick J Morton, Antentor Hinton

The success of mentoring derives from active and respectful listening and the willingness to learn and accept opportunities for personal growth. This shapes every trainee and their destined path in science, technology, engineering, and mathematics (STEM). The act of cultivating rapport, asking, and pondering meaningful questions, and receiving constructive feedback are critical to support a productive mentoring relationship. Successful mentoring in STEM can be established and allow mentees, especially underrepresented minorities (URMs), to flourish in an environment where they feel welcomed and supported. However, mentees from underrepresented groups often experience inadequate mentoring due to a mentor's lack of awareness, poor trainings themselves, or lack of understanding of the mentee's hardships. It is important for mentors and mentees to work together to promote diversity, equity, and inclusion (DEI) in STEM education through creativity, authenticity, and networking. We analyzed data obtained from students who attended a recent workshop that are interested in going to graduate school. Our results show that despite low initial expectations for the workshop, many students were satisfied in the knowledge they gleaned. The future and role of diversity in STEM within these underrepresented groups lies in community support and an important role that they can play in the lives of others through DEI initiatives and throughout their careers all of which involves positive mentoring.

师徒关系的成功源于积极和尊重的倾听,以及学习和接受个人成长机会的意愿。这决定了每一位学员及其在科学、技术、工程和数学(STEM)领域的发展方向。培养融洽的关系,提出和思考有意义的问题,以及接受建设性的反馈,对于支持富有成效的师徒关系至关重要。可以建立成功的STEM指导,并允许被指导者,特别是代表性不足的少数民族(urm),在他们感到受欢迎和支持的环境中蓬勃发展。然而,来自代表性不足的群体的被指导者往往由于导师缺乏意识、自身培训不足或缺乏对被指导者困难的理解而经历不足的指导。重要的是,导师和学员要共同努力,通过创造力、真实性和网络,促进STEM教育中的多样性、公平性和包容性(DEI)。我们分析了从最近参加了一个有兴趣读研的研讨会的学生那里获得的数据。我们的结果显示,尽管对研讨会的最初期望较低,但许多学生对他们收集的知识感到满意。在这些代表性不足的群体中,STEM多样性的未来和作用在于社区支持,以及他们可以通过DEI倡议和整个职业生涯在他人生活中发挥的重要作用,所有这些都涉及到积极的指导。
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引用次数: 1
An effective workshop on "How to be an Effective Mentor for Underrepresented STEM Trainees". 一个关于“如何成为STEM受训者的有效导师”的有效研讨会。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-07-06 DOI: 10.1093/femspd/ftac022
Andrea G Marshall, Zer Vue, Caroline B Palavicino-Maggio, Kit Neikirk, Heather K Beasley, Edgar Garza-Lopez, Sandra A Murray, Denise Martinez, Amber Crabtree, Zachary C Conley, Larry Vang, Jamaine S Davis, Keesha L Powell-Roach, Susan Campbell, Lillian J Brady, Angyth B Dal, Bryanna Shao, Stefanie Alexander, Nancy Vang, Neng Vue, Mein Vue, Haysetta D Shuler, Elsie C Spencer, Derrick J Morton, Antentor Hinton

Despite an increase in programming to promote persons excluded by their ethnicity or race (PEER) scholars, minorities remain underrepresented in many STEM programs. The academic pipeline is largely leaky for underrepresented minority (URM) scholars due to a lack of effective mentorship. Many URM students experience microaggressions and discrimination from their mentors due to a lack of quality mentorship training. In this workshop, we provide a framework to show trainees what effective mentoring looks like. Mentees, especially URM trainees, can flourish in effective mentoring environments where they feel welcomed and can comfortably develop new ideas without feeling threatened by external factors. Effective mentoring environments provide motivational support, empathy, cultural competency, and training. This workshop explains facets of effective mentoring to students, as well as highlights to URM trainees why mentors can serve as valuable resources.

尽管促进被种族或种族(PEER)学者排斥的人的项目有所增加,但少数族裔在许多STEM项目中的代表性仍然不足。由于缺乏有效的指导,少数族裔(URM)学者的学术渠道在很大程度上存在漏洞。由于缺乏高质量的导师培训,许多URM学生经历了导师的微侵犯和歧视。在这个研讨会中,我们提供了一个框架,向学员展示有效的指导是什么样子的。学员,特别是URM学员,可以在有效的指导环境中茁壮成长,在那里他们感到受欢迎,可以轻松地发展新想法,而不会感到受到外部因素的威胁。有效的指导环境提供动机支持、移情、文化能力和培训。这个工作坊向学生解释有效辅导的各个方面,并向URM学员强调为什么导师可以成为宝贵的资源。
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引用次数: 1
Expression of concern on: Mitogen-activated protein kinases regulate Mycobacterium avium-induced tumor necrosis factor-α release from macrophages. 对丝裂原活化蛋白激酶调控巨噬细胞释放瘤坏死因子α的关注
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-06-22 DOI: 10.1093/femspd/ftac017
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引用次数: 7
Coexistence of blaNDM-1, blaOXA-51, blaOXA-23 and armA in conjunction with novel mutations detected in RND efflux pump regulators in tigecycline resistant clinical isolates of Acinetobacter baumannii. 在对替加环素耐药的鲍曼不动杆菌临床分离株中检测到blaNDM-1、blaOXA-51、blaOXA-23和armA的共存以及RND外排泵调节因子的新突变。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-06-15 DOI: 10.1093/femspd/ftac020
A. Sawant, Sudhakar Pagal, Ashutosh Kumar Amar, L. Panda, S. Devi C., P. Shashikala, R. Kanungo, K. Prashanth
This study has investigated a total of 51 A. baumannii isolates for the prevalence of resistant determinants in tigecycline susceptible and non-susceptible clinical isolates of A. baumannii. Antimicrobial susceptibility testing revealed 74% of isolates were tigecycline resistant. Mutations in RND-efflux pump regulatory genes and the expression of efflux pump genes were measured in tigecycline resistant isolates. There was a strong co-relation between the blaNDM-1 and armA wherein majority of the isolates that are positive for blaNDM-1 have also harbored armA. Compared with TSAB (tigecycline susceptible A. baumannii), TNAB (tigecycline non-susceptible A. baumannii) isolates show increased distribution of blaNDM-1 (p = 0.048), blaIMP-1 (p<0.0001) and blaOXA-51 (p = 0.0029) carbapenemase genes. The variants of RND-efflux pump regulatory genes due to amino-acid mutations in adeS (F12S, K84E, W61R, N268H and Q299R) and adeL (G21R and Q262R) were identified in tigecycline resistant isolates as well as ISAba1 mediated disruption of adeN were observed causing overexpression of adeIJK efflux pump. Additionally, mutations in adeRS were also associated with increased expression of adeABC efflux pump. Besides, TNAB isolates showed significantly (p<0.0001) higher ability of biofilm formation as compared to TSAB isolates. The tigecycline resistance due to mutations in contemporary A. baumannii isolates having a higher ability to form biofilm may pose therapeutic difficulties.
本研究调查了51个鲍曼不动杆菌分离株在替加环素敏感和非敏感鲍曼不动杆菌临床分离株中耐药决定因素的患病率。药敏试验显示74%的分离株对替加环素耐药。在替加环素耐药菌株中检测了rnd -外排泵调控基因的突变和外排泵基因的表达。blaNDM-1和armA之间有很强的相关性,其中大多数blaNDM-1阳性的分离株也携带armA。与TSAB(替加环素敏感型鲍曼不敏感型鲍曼不动杆菌)相比,TNAB(替加环素不敏感型鲍曼不动杆菌)分离株的碳青霉烯酶基因blaNDM-1 (p = 0.048)、blaIMP-1 (p<0.0001)和blaOXA-51 (p = 0.0029)分布增加。在替加环素耐药菌株中发现了adeS (F12S、K84E、W61R、N268H和Q299R)和adeL (G21R和Q262R)氨基酸突变导致的rnd -外排泵调控基因变异,并观察到ISAba1介导的adeN破坏导致adeIJK外排泵过表达。此外,ader的突变也与adeABC外排泵的表达增加有关。此外,TNAB菌株的生物膜形成能力显著高于TSAB菌株(p<0.0001)。当代鲍曼不动杆菌分离株具有较高的生物膜形成能力,其突变导致的替加环素耐药性可能会给治疗带来困难。
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引用次数: 1
Immunopotentiation by linking Hsp70 T-cell epitopes to Gag-Pol-Env-Nef-Rev multiepitope construct and increased IFN-gamma secretion in infected lymphocytes. 通过将Hsp70 T细胞表位连接到Gag-Pol-Ev-Nef-Rev多表位构建体来增强免疫,并增加感染淋巴细胞中的IFN-γ分泌。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-06-15 DOI: 10.1093/femspd/ftac021
E. Akbari, S. Ajdary, E. M. Ardakani, Elnaz Agi, A. Milani, Masoud Seyedinkhorasani, V. Khalaj, A. Bolhassani
Therapeutic human immunodeficiency virus (HIV) vaccines can boost the anti-HIV host immunity to control viral replication and eliminate viral reservoirs in the absence of anti-retroviral therapy. In this study, two computationally designed multiepitope Gag-Pol-Env-Nef-Rev and Hsp70-Gag-Pol-Env-Nef-Rev constructs harboring immunogenic and highly conserved HIV T cell epitopes were generated in E. coli as polypeptide vaccine candidates. Furthermore, the multiepitope gag-pol-env-nef-rev and hsp70-gag-pol-env-nef-rev DNA vaccine constructs were prepared and complexed with MPG cell-penetrating peptide. The immunogenicity of the multiepitope constructs were evaluated using the homologous and heterologous prime/boost strategies in mice. Moreover, the secretion of IFN-γ was assessed in infected lymphocytes in vitro. Our data showed that the homologous polypeptide regimens could significantly induce a mixture of IgG1 and IgG2a antibody responses, activate T cells to secret IFN-γ, IL-5, IL-10, and generate Granzyme B. Moreover, IFN-γ secretion was significantly enhanced in single-cycle replicable (SCR) HIV-1 virions-infected splenocytes in these groups compared to uninfected splenocytes. The linkage of heat shock protein 70 (Hsp70) epitopes to Gag-Pol-Env-Nef-Rev polypeptide in the homologous regimen increased significantly cytokines and Granzyme B levels, and IFN-γ secretion in virions-infected splenocytes. Briefly, both designed constructs in the homologous regimens can be used as a promising vaccine candidate against HIV infection.
治疗性人类免疫缺陷病毒(HIV)疫苗可以在没有抗逆转录病毒治疗的情况下增强抗HIV宿主的免疫力,以控制病毒复制并消除病毒库。在这项研究中,计算设计了两个多表位Gag-Pol-Env-Nef-Rev和Hsp70-Gag-Pol-Env-Nef-Rev构建物,其中包含免疫原性和高度保守的HIV T细胞表位,作为多肽疫苗候选物在大肠杆菌中产生。此外,制备了多表位gag-pol-env-nef-rev和hsp70-gag-pol-env-nef-rev DNA疫苗构建物,并与MPG细胞穿透肽络合。采用同源和异源启动/增强策略对构建的多表位进行免疫原性评价。此外,体外检测感染淋巴细胞中IFN-γ的分泌情况。我们的数据显示,同源多肽方案可以显著诱导IgG1和IgG2a抗体的混合反应,激活T细胞分泌IFN-γ、IL-5、IL-10,并产生颗粒酶b。此外,与未感染的脾细胞相比,这些组中单周期可复制(SCR) HIV-1病毒粒子感染的脾细胞中IFN-γ分泌显著增强。在同源方案中,热休克蛋白70 (Hsp70)表位与Gag-Pol-Env-Nef-Rev多肽连锁可显著增加病毒粒子感染的脾细胞中细胞因子和颗粒酶B水平以及IFN-γ的分泌。简而言之,在同源方案中设计的两种结构都可以用作抗HIV感染的有希望的候选疫苗。
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引用次数: 1
P. falciparum PfRUVBL proteins binds at TARE region and var gene promoter located in subtelomeric region. 恶性疟原虫PfRUVBL蛋白结合于TARE区,var基因启动子位于亚端粒区。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-05-31 DOI: 10.1093/femspd/ftac018
H. Saxena, Ashish Gupta
In order to survive and establish infection, Plasmodium parasite employ various strategies to evade host immune response. Var genes family, a repertoire of 60 genes, express parasite-specific protein PfEMP1, a variable surface antigen, on the membrane of infected erythrocyte, and by continuously switching the variants of PfEMP1, helps the parasite to avoid detection and destruction by host immune system during intra-erythrocytic developmental cycle. Although chromatin modifications are recognized to be a prominent phenomenon in regulation of mono-allelic expression of these var genes, however the precise histone codes and molecular players & mechanisms guiding these modifications are yet to be unravelled in depth. In this study, we have functionally characterized RUVBL proteins of P. falciparum and shown that PfMYST (an essential lysine acetyl transferase) and PfRUVBL protein complex occupy the TARE region and var gene promoter in ring stage of the parasite. Further we have demonstrated that PfMYST/PfRUVBL complex interact with core histone, H3 & H4. Overall the findings of this study adds a layer by identifying the potential role of epigenetic regulators, PfMYST & PfRUVBL in regulation of monoallelic expression of var genes in malaria parasite.
为了生存和建立感染,疟原虫采用各种策略来逃避宿主的免疫反应。Var基因家族共有60个基因,在被感染的红细胞膜上表达寄生虫特异性蛋白PfEMP1,这是一种可变的表面抗原,通过不断切换PfEMP1的变体,帮助寄生虫在红细胞内发育周期中避免宿主免疫系统的检测和破坏。虽然染色质修饰被认为是调控这些变异基因单等位基因表达的一个突出现象,但指导这些修饰的精确组蛋白编码和分子参与者和机制尚未深入揭示。在这项研究中,我们对恶性疟原虫的RUVBL蛋白进行了功能表征,发现PfMYST(一种必需赖氨酸乙酰转移酶)和PfRUVBL蛋白复合物占据了疟原虫环期的TARE区和var基因启动子。此外,我们已经证明PfMYST/PfRUVBL复合物与核心组蛋白H3和H4相互作用。总的来说,本研究的发现通过确定表观遗传调节因子PfMYST和PfRUVBL在调节疟疾寄生虫var基因单等位基因表达中的潜在作用,增加了一层。
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引用次数: 2
AZI2 positively regulates the induction of type I interferon in influenza-trigger pediatric pneumonia. AZI2正调控I型干扰素在流感引发的儿童肺炎中的诱导作用。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-05-20 DOI: 10.1093/femspd/ftac016
Meili Wei, Ya-nan Zheng, Jing Xu, Qiwei Sun
5-azacytidine-induced protein 2 (AZI2) is known to have a crucial role in antiviral innate immunity. This study aims to explore the roles of AZI2 in influenza-trigger pediatric pneumonia and its molecular mechanism. qPCR and immunoblotting assays were used to determine the levels of target genes and proteins. The lung infection mouse model was established by using PR8 H1N1 virus in AZI2 germline knockout (AZI2-/-) and wide-type (WT) mice. In addition, HEK293T cell-based luciferase reporter assays were used to investigate the regulatory effects of AZI2 on type I interferon. Immune precipitation and immunofluorescence staining were used to evaluate the interactions between AZI2 and TANK binding kinase 1 (TBK1). We observed an elevation in the expressions of IFN-I and AZI2 in peripheral blood mononuclear cells from the pneumonia patients with mild symptoms. Interestingly, AZI2 deficiency deteriorated the influenza-induced pathological symptoms in the lung as well as reduced the survival rate. It was further showed that AZI2 positively regulated the expressions of type I interferon, inflammatory cytokines, and IFN production-related genes. The molecular mechanism data revealed that AZI2 regulated the interactions between TBK1 and TANK. In summary, AZI2 positively regulates type I interferon production in influenza-induced pediatric pneumonia by promoting the interactions between TBK1 and TANK.
5-氮胞苷诱导蛋白2 (AZI2)在抗病毒先天免疫中起着至关重要的作用。本研究旨在探讨AZI2在流感引发的儿童肺炎中的作用及其分子机制。采用qPCR和免疫印迹法测定靶基因和蛋白的水平。采用PR8 H1N1病毒在AZI2胚系敲除(AZI2-/-)和广型(WT)小鼠中建立肺部感染小鼠模型。此外,以HEK293T细胞为基础的荧光素酶报告基因法研究AZI2对I型干扰素的调控作用。采用免疫沉淀法和免疫荧光染色法评价AZI2与TANK结合激酶1 (TBK1)的相互作用。我们观察到轻症状肺炎患者外周血单个核细胞中IFN-I和AZI2的表达升高。有趣的是,AZI2缺乏恶化了流感引起的肺部病理症状,并降低了生存率。进一步表明AZI2正调控I型干扰素、炎症因子和IFN产生相关基因的表达。分子机制数据显示AZI2调控TBK1与TANK的相互作用。综上所述,AZI2通过促进TBK1和TANK之间的相互作用,积极调节流感诱导的儿童肺炎中I型干扰素的产生。
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引用次数: 2
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Pathogens and disease
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