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First molecular detection of Entamoeba gingivalis subtypes in individuals from Turkey. 首次在土耳其个体中进行齿龈内阿米巴亚型的分子检测。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad017
Serra Örsten, Cem Şahin, Engin Yılmaz, Yakut Akyön

Entamoeba gingivalis is a parasitic protozoan that colonizes the human oral cavity and there are two subtypes (ST1 and ST2) that have been identified to date. However, there are no reports on the molecular detection or characterization of E. gingivalis in Turkey. The objective of this study was to detect the presence of E. gingivalis in Turkish healthy individuals and those with periodontal disease and to subtype the isolates using molecular techniques. Samples from the oral cavity of 94 individuals were taken and the presence of E. gingivalis was determined by PCR using primers for SsrRNA and the amplicons were then confirmed by DNA sequencing. Each participant completed a questionnaire that included demographic data, habits and lifestyle, as well as health status. The presence of E. gingivalis was detected in a total of 19 samples (11 patients and eight healthy individuals). Molecular characterization determined that 12 samples belonged to ST1 and seven samples belonged to ST2. The presence of E. gingivalis was higher in patients with periodontal disease than in healthy individuals, and this association was statistically significant (P < .05). This study constitutes the first report of molecular detection and subtyping of E. gingivalis in Turkey.

牙龈内阿米巴是一种寄生在人类口腔中的原生动物,目前已确定有两种亚型(ST1和ST2)。然而,目前还没有关于在土耳其检测或鉴定牙龈杆菌的分子的报告。本研究的目的是检测土耳其健康人和牙周病患者中是否存在牙龈卟啉单胞菌,并使用分子技术对分离株进行亚型。从94个个体的口腔中采集样本,并通过使用SsrRNA引物的PCR来确定牙龈杆菌的存在,然后通过DNA测序来确认扩增子。每个参与者都完成了一份问卷,其中包括人口统计数据、习惯和生活方式以及健康状况。在总共19个样本(11名患者和8名健康人)中检测到牙龈E。分子表征确定12个样品属于ST1,7个样品属于ST 2。患有牙周病的患者牙龈卟啉单胞菌的存在率高于健康人,这种相关性具有统计学意义(P
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引用次数: 0
Nur77 influences immunometabolism to regulate the release of proinflammatory cytokines and the formation of lipid bodies during Mycobacterium tuberculosis infection of macrophages. Nur77在结核分枝杆菌感染巨噬细胞过程中影响免疫代谢,调节促炎细胞因子的释放和脂质体的形成。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad033
Pankaj Birari, Soumya Mal, Debayan Majumder, Arun K Sharma, Manish Kumar, Troyee Das, Zhumur Ghosh, Kuladip Jana, Umesh D Gupta, Manikuntala Kundu, Joyoti Basu

Infection of macrophages with Mycobacterium tuberculosis induces innate immune responses designed to clear the invading bacterium. However, bacteria often survive within the intracellular environment by exploiting these responses triggered by macrophages. Here, the role of the orphan nuclear receptor Nur77 (Nr4a1) in regulating the response of macrophages infected with M. tuberculosis (Mtb) has been delineated. Nur77 is induced early during infection, regulates metabolism by binding directly at the promoter of the TCA cycle enzyme, isocitrate dehydrogenase 2 (IDH2), to act as its repressor, and shifts the balance from a proinflammatory to an anti-inflammatory phenotype. Depletion of Nur77 increased transcription of IDH2 and, consequently, the levels of intracellular succinate, leading to enhanced levels of the proinflammatory cytokine IL-1β. Further, Nur77 inhibited the production of antibacterial nitric oxide and IL-1β in a succinate dehydrogenase (SDH)-dependent manner, suggesting that its induction favors bacterial survival by suppressing bactericidal responses. Indeed, depletion of Nur77 inhibited the intracellular survival of Mtb. On the other hand, depletion of Nur77 enhanced lipid body formation, suggesting that the fall in Nur77 levels as infection progresses likely favors foamy macrophage formation and long-term survival of Mtb in the host milieu.

巨噬细胞感染结核分枝杆菌诱导先天免疫反应,旨在清除入侵的细菌。然而,细菌通常通过利用巨噬细胞引发的这些反应在细胞内环境中生存。本文描述了孤儿核受体Nur77 (Nr4a1)在调节感染结核分枝杆菌的巨噬细胞反应中的作用。Nur77在感染早期被诱导,通过直接结合TCA循环酶的启动子来调节代谢,异柠檬酸脱氢酶2 (IDH2)作为其抑制因子,并将平衡从促炎表型转变为抗炎表型,Nur77的缺失增加了IDH2的转录,因此,细胞内的丁二酸水平导致促炎细胞因子IL-1β水平的提高。此外,Nur77以琥珀酸脱氢酶(SDH)依赖的方式抑制抗菌一氧化氮和IL-1β的产生,表明其诱导作用通过抑制杀菌反应促进细菌存活。事实上,Nur77的缺失抑制了结核分枝杆菌的细胞内存活。另一方面,Nur77的缺失增强了脂质体的形成,这表明随着感染的进展,Nur77水平的下降可能有利于泡沫巨噬细胞的形成和结核分枝杆菌在宿主环境中的长期存活。
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引用次数: 0
Impact of nutrients on the function of the chlamydial Rsb partner switching mechanism. 营养物质对衣原体Rsb伴侣转换机制功能的影响。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-11-29 DOI: 10.1093/femspd/ftac044
Shiomi Kuwabara, Evan R Landers, Derek J Fisher

The obligate intracellular bacterial pathogen Chlamydia trachomatis is a leading cause of sexually transmitted infections and infectious blindness. Chlamydia undergo a biphasic developmental cycle alternating between the infectious elementary body (EB) and the replicative reticulate body (RB). The molecular mechanisms governing RB growth and RB-EB differentiation are unclear. We hypothesize that the bacterium senses host cell and bacterial energy levels and metabolites to ensure that development and growth coincide with nutrient availability. We predict that a partner switching mechanism (PSM) plays a key role in the sensing and response process acting as a molecular throttle sensitive to metabolite levels. Using purified wild type and mutant PSM proteins, we discovered that metal type impacts enzyme activity and the substrate specificity of RsbU and that RsbW prefers ATP over GTP as a phosphate donor. Immunoblotting analysis of RsbV1/V2 demonstrated the presence of both proteins beyond 20 hours post infection and we observed that an RsbV1-null strain has a developmental delay and exhibits differential growth attenuation in response to glucose levels. Collectively, our data support that the PSM regulates growth in response to metabolites and further defines biochemical features governing PSM-component interactions which could help in the development of novel PSM-targeted therapeutics.

专性细胞内细菌病原体沙眼衣原体是性传播感染和感染性失明的主要原因。衣原体在感染性初级体(EB)和复制网状体(RB)之间交替进行双相发育周期。调控RB生长和RB- eb分化的分子机制尚不清楚。我们假设细菌感知宿主细胞和细菌的能量水平和代谢物,以确保发育和生长与营养供应一致。我们预测伴侣转换机制(PSM)在感知和响应过程中发挥关键作用,作为对代谢物水平敏感的分子油门。使用纯化的野生型和突变型PSM蛋白,我们发现金属型影响RsbU的酶活性和底物特异性,并且RsbW更倾向于ATP而不是GTP作为磷酸供体。RsbV1/V2的免疫印迹分析表明,在感染后20小时后,这两种蛋白都存在,我们观察到RsbV1-null菌株具有发育延迟,并且在葡萄糖水平的反应中表现出不同的生长衰减。总的来说,我们的数据支持PSM调节代谢产物的生长,并进一步定义了控制PSM-成分相互作用的生化特征,这可能有助于开发新的PSM靶向治疗方法。
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引用次数: 0
Adjuvants to increase immunogenicity of SARS-CoV-2 RBD and support maternal-fetal transference of antibodies in mice. 佐剂增加SARS-CoV-2 RBD的免疫原性并支持小鼠抗体的母胎转移
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-10-19 DOI: 10.1093/femspd/ftac038
Gabrielle Gimenes Lima, Amanda Izeli Portilho, Elizabeth De Gaspari

Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women-to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.

佐剂是疫苗的重要组成部分,增加免疫原性和调节免疫反应。目前仍在开发SARS-CoV-2疫苗,以改善全球免疫接种的可及性。这些调查应针对特定人群,如孕妇,以保护母亲和新生儿。本研究用DDA和皂苷混合佐剂免疫雌性成年小鼠的SARS-CoV-2受体结合域(Receptor-binding domain, RBD),并进行交配,以验证IgG的母体转移性。相比之下,另一组接受脑膜炎奈瑟菌和明矾的omv佐剂的RBD。佐剂增强IgG的产生和中和。DDA/Sap增加了IgG1、IgG2a、IgG2b和IgG3同型。总IgG贪婪度高,IgG1、IgG2a和IgG2b贪婪度也高。IgG抗体被有效地转移到子代,主要是IgG2a、IgG2b和IgG3。被动转移免疫球蛋白虽失去活性,但仍保持中和能力。采用Dot-ELISA和免疫印迹法对ELISA数据进行验证。DDA和皂苷似乎是一种很有前途的佐剂混合物,可以增强SARS-CoV-2抗原的体液反应。无论COVID-19疫苗使用何种平台,都需要进一步研究母体免疫在保护后代方面的作用。
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引用次数: 0
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
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Pathogens and disease
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