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Development of the novel gene chip and restriction fragment length polymorphism (RFLP) methods for rapid detection of Mycobacterium tuberculosis complex in broth culture 开发新型基因芯片和限制性片段长度多态性(RFLP)方法,用于肉汤培养液中结核分枝杆菌复合体的快速检测。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.09.003
Wen-Hung Wang , Chun-Yu Lin , Shu-Huei Jain , Po-Liang Lu , Yen-Hsu Chen

Background

Tuberculosis (TB) is a major global public health issue. Prompt and accurate TB diagnosis is crucial for starting appropriate treatments and preventing the disease's spread. Current diagnostic techniques are either slow or expensive. This study aimed to create and evaluate a new, fast, highly reliable, and cost-effective TB detection method using a gene chip and Restriction Fragment Length Polymorphism (RFLP) analysis on Mycobacteria Growth Indicator Tubes (MGIT) specimens.

Methods

We assessed the effectiveness of a novel gene chip and RFLP methods targeting the 16S rRNA gene of Mycobacterium tuberculosis in 2000 MGIT culture-positive specimens. RFLP analysis identified the AfeI restriction site within the M. tuberculosis complex (MTBC) genome. Discrepancies were investigated through extensive sequencing and Cobas TaqMan PCR analysis, along with reviewing patient profiles.

Results

Both methods showed high efficacy in detecting MTBC in broth cultures, with the gene chip method achieving a sensitivity of 99.27 %, specificity of 98.35 %, and the RFLP method showing a sensitivity of 98.18 %, specificity of 99.31 %. False negatives in two isolates were due to a mutation in the AfeI site. Additionally, five cases showed MTBC presence when nontuberculous Mycobacterium species grew in cultures.

Conclusion

Our novel gene chip and RFLP methods are effective for rapid highly-reliable and cost-effective M. tuberculosis detection in MGIT specimens. Both gene chip and RFLP methods are suitable for resource-limited settings, offering an economical advantage. These methods have significant potential to improve clinical TB diagnosis.
背景:结核病(TB)是一个重大的全球公共卫生问题。及时准确的结核病诊断对于开始适当的治疗和防止疾病蔓延至关重要。目前的诊断技术要么缓慢,要么昂贵。本研究旨在利用基因芯片和对分枝杆菌生长指示管(MGIT)标本的限制性片段长度多态性(RFLP)分析,创建并评估一种新型、快速、高度可靠且经济高效的结核病检测方法:我们在 2000 份 MGIT 培养阳性标本中评估了针对结核分枝杆菌 16S rRNA 基因的新型基因芯片和 RFLP 方法的有效性。RFLP 分析确定了结核分枝杆菌复合体(MTBC)基因组中的 AfeI 限制位点。通过广泛的测序和 Cobas TaqMan PCR 分析,并查阅患者资料,对差异进行了调查:基因芯片法的灵敏度为 99.27%,特异性为 98.35%;RFLP 法的灵敏度为 98.18%,特异性为 99.31%。两个分离物的假阴性是由于 AfeI 位点发生了突变。此外,有五个病例在培养物中生长出非结核分枝杆菌时显示出 MTBC 的存在:结论:我们的新型基因芯片和 RFLP 方法可在 MGIT 标本中快速、高可靠、低成本地检测结核杆菌。基因芯片和 RFLP 方法都适用于资源有限的环境,具有经济优势。这些方法在改善临床结核病诊断方面具有巨大潜力。
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引用次数: 0
Forty years of HIV infection and AIDS in Taiwan: Reflection on the past and looking toward the future 台湾艾滋病毒感染和艾滋病四十年:回顾过去,展望未来。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.11.003
Sung-Hsi Huang , Hsun-Yin Huang , Stephane Wen-Wei Ku , Po-Hsien Kuo , Kuan-Yin Lin , Guan-Jhou Chen , Chia-Chi Lee , Yen-Fang Huang , Chien-Ching Hung
We review the epidemiology, policies, and control programs of HIV infection in Taiwan in the past 40 years since the first case of HIV infection was diagnosed in 1984. With the introduction of combination antiretroviral therapy (ART) in Taiwan in 1997, the incidences of HIV-related opportunistic illnesses and mortality have significantly declined. However, despite improved access to HIV testing and treatment, late presentation of HIV infection remains common. Unprotected sex, particularly among men who have sex with men, continues to be the leading risk for HIV transmission after implementation of harm reduction program to control an outbreak of HIV infection among people who inject drugs that occurred in 2003–2007. The sequential introduction of well-tolerated, effective, single-tablet antiretroviral regimens has facilitated the implementation of “treat-all” policy in 2016, rapid ART initiation within 7 days of diagnosis in 2018, and same-day ART initiation in 2021 when immunochromatography was used for rapid confirmation of HIV infection. Government-funded pilot program of pre-exposure prophylaxis for HIV infection, which was launched in 2016 followed by wider enrollment of people at high risk for HIV acquisition in 2018, have contributed to sustained declines of the incidence of HIV infection since 2018, along with high rates of linkage to HIV care, ART initiation, viral suppression, and retention in care in Taiwan. Challenges remain to achieve HIV elimination and long-term successful management of HIV infection, which include stigma and discrimination, late presentation of HIV infection, and accelerated ageing with increasing rates of co-morbidities among people with HIV.
我们回顾了自 1984 年台湾确诊首例 HIV 感染病例以来的 40 年间,台湾 HIV 感染的流行病学、政策和控制计划。随着 1997 年台湾引入抗逆转录病毒联合疗法(ART),与 HIV 相关的机会性疾病发病率和死亡率显著下降。然而,尽管获得 HIV 检测和治疗的机会增加了,但晚期感染 HIV 的情况仍然很普遍。2003-2007 年,为控制注射吸毒者中艾滋病毒感染的爆发,实施了减少伤害计划,但无保护性行为,尤其是男男性行为者中的无保护性行为,仍是艾滋病毒传播的主要风险。依次引入耐受性好、有效的单片抗逆转录病毒疗法,促进了 2016 年 "全治疗 "政策的实施,2018 年在确诊后 7 天内快速启动抗逆转录病毒疗法,2021 年在使用免疫层析技术快速确认艾滋病毒感染时,当天启动抗逆转录病毒疗法。政府资助的艾滋病毒感染暴露前预防试点项目于 2016 年启动,随后于 2018 年扩大了艾滋病毒感染高危人群的招募范围,这些措施促使台湾的艾滋病毒感染率自 2018 年以来持续下降,同时,台湾的艾滋病毒关怀链接率、抗逆转录病毒疗法启动率、病毒抑制率和关怀保留率也很高。实现消除艾滋病毒和长期成功管理艾滋病毒感染仍面临挑战,其中包括污名化和歧视、艾滋病毒感染出现较晚、老龄化加速以及艾滋病毒感染者共病率增加。
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引用次数: 0
Corrigendum to “Influenza and the risk of active tuberculosis occurrence among individuals with latent tuberculosis infection: A national cohort study in South Korea (2015–2020)” [J Microbiol Immunol Infect 57 (2024) 437–445 JOUMII-D-23-00515R1] “流感与潜伏结核感染个体活动性结核病发生风险:韩国国家队列研究(2015-2020)”的勘误表[J].中华微生物学杂志,2004,22(4):437-445。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.12.001
Jaehee Lee , Hyewon Seo , Dohyang Kim , Jinseub Hwang , Jin-Won Kwon
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引用次数: 0
High hemolytic activity in Staphylococcus aureus t1081/ST45 due to increased hla protein production and potential RNAIII-independent regulation 金黄色葡萄球菌 t1081/ST45 的高溶血活性是由于 hla 蛋白生成增加和潜在的 RNAIII 非依赖性调控所致。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.09.005
Yu-Tzu Lin , Ngoc-Niem Bui , Yu-Syuan Cheng , Cheng-Wen Lin , Chun-Li Lee , Tai-Fen Lee , Po-Ren Hsueh

Background

α-Hemolysin, encoded by hla, is a major virulence factor of Staphylococcus aureus. Sequence type (ST) 45 is a globally spread clone with increasing clinical prevalence in Taiwan. Our previous study showed that among the CC45 isolates, the spa type t1081 isolates presented greater hemolytic activity.

Materials and methods

The hemolytic activity of 67 CC45 isolates (44 t1081 and 23 non-t1081) from clinical blood cultures was assessed using rabbit red blood cells. The sequences of hla and its upstream regulatory regions and RNAIII were compared between the two groups. The expression of hla and its regulators RNAIII, mgrA, and saeR was analyzed via qRT‒PCR, while Hla protein levels were measured via Western blotting.

Results

Compared with non-t1081 isolates, t1081 isolates presented increased hemolytic activity. No significant differences in hla sequences, upstream regulatory regions, or gene expression levels were detected between the two groups. The expression of the transcriptional regulators mgrA and saeR was also similar between the two groups. Western blotting revealed increased Hla protein in the t1081 isolates. However, neither the sequence or expression of RNAIII, a regulator of hla at both the transcriptional and posttranscriptional levels, differed between the groups.

Conclusion

Our study revealed that, compared with other CC45 isolates, the t1081/ST45 isolates presented greater hemolytic activity. This heightened activity was due mainly to increased Hla protein levels. Moreover, the higher translation levels may be independent of the known regulator RNAIII, indicating a potential RNAIII-independent mechanism for Hla regulation.
背景:由 hla 编码的 α 溶血素是金黄色葡萄球菌的主要毒力因子。序列类型(ST)45 是一种全球传播的克隆,在台湾的临床流行率越来越高。我们之前的研究表明,在 CC45 分离物中,t1081 型 spa 分离物具有更强的溶血活性:用兔红细胞评估了临床血液培养物中 67 个 CC45 分离物(44 个 t1081 型和 23 个非 t1081 型)的溶血活性。比较了两组细胞中 hla 及其上游调控区和 RNAIII 的序列。通过 qRT-PCR 分析了 hla 及其调控因子 RNAIII、mgrA 和 saeR 的表达,并通过 Western 印迹检测了 Hla 蛋白水平:结果:与非 t1081 分离物相比,t1081 分离物的溶血活性增强。两组分离物的 hla 序列、上游调控区和基因表达水平均无明显差异。两组之间转录调控因子 mgrA 和 saeR 的表达也相似。Western 印迹显示,t1081 分离物中的 Hla 蛋白增加了。然而,RNAIII(hla 在转录和转录后水平的调控因子)的序列和表达在两组间均无差异:我们的研究表明,与其他 CC45 分离物相比,t1081/ST45 分离物具有更强的溶血活性。这种活性的增强主要是由于 Hla 蛋白水平的提高。此外,较高的翻译水平可能与已知的调节因子 RNAIII 无关,这表明 Hla 的调节机制可能与 RNAIII 无关。
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引用次数: 0
Interaction of human neutrophils with Trichomonas vaginalis protozoan highlights lactoferrin secretion 人类中性粒细胞与阴道毛滴虫原生动物的相互作用凸显了乳铁蛋白的分泌。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.11.004
Wei-Hung Cheng , Ruei-Min Chen , Seow-Chin Ong , Yuan-Ming Yeh , Po-Jung Huang , Chi-Ching Lee

Background

Neutrophils are vital constituents of the immune response in the vaginal environment, playing a pivotal role in the defense against trichomoniasis. Earlier studies have shown that Trichomonas vaginalis (T. vaginalis) can release leukotriene B4 (LTB4), a molecule that attracts and activates neutrophils. Additionally, secretory products from this parasite can induce the production of interleukin-8 (IL-8) in mast cells and neutrophils, which further recruits neutrophils to the infection site. The precise reasons behind T. vaginalis actively promoting interaction between parasites and neutrophils rather than inhibiting the inflammatory response remain unclear.

Results

In this study, we collected conditioned medium to elucidate the intricate dynamics between T. vaginalis and human neutrophils. We conducted a comprehensive profiling of soluble excretory/secretory proteins (ESPs), identifying 192 protein spots, of which 94 were successfully characterized through mass spectrometry analysis. Notably, the majority of induced ESPs from co-cultivation exhibited consistency with the trichomonad and neutrophil standalone groups, except for lactoferrin, which was observed exclusively following the interaction between neutrophils and T. vaginalis. The secretion of lactoferrin was determined to be a contact-dependent process. It was interesting to identify the ability of the iron-loaded lactoferrin to extend the survival time of T. vaginalis under iron-deficient conditions.

Conclusions

This study represents the first to identify the origin of lactoferrin during T. vaginalis infection, shedding light on the potential reason for T. vaginalis's ability to attract neutrophils to the infection site: the acquisition of the iron source, lactoferrin.
背景:中性粒细胞是阴道环境中免疫反应的重要组成部分,在防御滴虫病方面发挥着关键作用。早期的研究表明,阴道毛滴虫(T. vaginalis)能释放白三烯 B4(LTB4),这是一种能吸引和激活中性粒细胞的分子。此外,这种寄生虫的分泌物还能诱导肥大细胞和中性粒细胞产生白细胞介素-8(IL-8),从而进一步将中性粒细胞吸引到感染部位。阴道球菌积极促进寄生虫与中性粒细胞之间的相互作用而非抑制炎症反应的确切原因尚不清楚:在这项研究中,我们收集了条件培养基,以阐明阴道球菌与人类中性粒细胞之间错综复杂的动态关系。我们对可溶性排泄/分泌蛋白(ESPs)进行了全面分析,确定了 192 个蛋白点,并通过质谱分析成功确定了其中 94 个蛋白点的特征。值得注意的是,除乳铁蛋白外,大多数共培养诱导的 ESP 与滴虫组和中性粒细胞独立组表现出一致性,而乳铁蛋白仅在中性粒细胞与阴道毛滴虫相互作用后才被观察到。乳铁蛋白的分泌被确定为是一个依赖接触的过程。有趣的是,在缺铁条件下,含铁的乳铁蛋白能够延长阴道球菌的存活时间:这项研究首次确定了阴道球菌感染过程中乳铁蛋白的来源,揭示了阴道球菌吸引中性粒细胞到感染部位的潜在原因:获取铁源--乳铁蛋白。
{"title":"Interaction of human neutrophils with Trichomonas vaginalis protozoan highlights lactoferrin secretion","authors":"Wei-Hung Cheng ,&nbsp;Ruei-Min Chen ,&nbsp;Seow-Chin Ong ,&nbsp;Yuan-Ming Yeh ,&nbsp;Po-Jung Huang ,&nbsp;Chi-Ching Lee","doi":"10.1016/j.jmii.2024.11.004","DOIUrl":"10.1016/j.jmii.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Neutrophils are vital constituents of the immune response in the vaginal environment, playing a pivotal role in the defense against trichomoniasis. Earlier studies have shown that <em>Trichomonas vaginalis</em> (<em>T. vaginalis</em>) can release leukotriene B4 (LTB4), a molecule that attracts and activates neutrophils. Additionally, secretory products from this parasite can induce the production of interleukin-8 (IL-8) in mast cells and neutrophils, which further recruits neutrophils to the infection site. The precise reasons behind <em>T. vaginalis</em> actively promoting interaction between parasites and neutrophils rather than inhibiting the inflammatory response remain unclear.</div></div><div><h3>Results</h3><div>In this study, we collected conditioned medium to elucidate the intricate dynamics between <em>T. vaginalis</em> and human neutrophils. We conducted a comprehensive profiling of soluble excretory/secretory proteins (ESPs), identifying 192 protein spots, of which 94 were successfully characterized through mass spectrometry analysis. Notably, the majority of induced ESPs from co-cultivation exhibited consistency with the trichomonad and neutrophil standalone groups, except for lactoferrin, which was observed exclusively following the interaction between neutrophils and <em>T. vaginalis</em>. The secretion of lactoferrin was determined to be a contact-dependent process. It was interesting to identify the ability of the iron-loaded lactoferrin to extend the survival time of <em>T. vaginalis</em> under iron-deficient conditions.</div></div><div><h3>Conclusions</h3><div>This study represents the first to identify the origin of lactoferrin during <em>T. vaginalis</em> infection, shedding light on the potential reason for <em>T. vaginalis</em>'s ability to attract neutrophils to the infection site: the acquisition of the iron source, lactoferrin.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"58 1","pages":"Pages 138-147"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction model, risk factor score and ventilator-associated pneumonia: A two-stage case-control study 预测模型、风险因素评分和呼吸机相关肺炎:两阶段病例对照研究。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.11.005
Hua Meng , Yuxin Shi , Kaming Xue , Di Liu , Xiongjing Cao , Yanyan Wu , Yunzhou Fan , Fang Gao , Ming Zhu , Lijuan Xiong

Background

Ventilator-associated pneumonia (VAP) is one of the most important hospital acquired infections in patients requiring mechanical ventilation (MV) in the intensive care unit, but the effective and robust predictable tools for VAP prevention were relatively lacked.

Methods

This study aimed to establish a weighted risk scoring system to examine VAP risk among a two-stage VAP case-control study, and to evaluate the diagnostic performance of risk factor score (RFS) for VAP. We constructed a prediction model by least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (XGBoost) models in 363 patients and 363 controls, and weighted RFS was calculated based on significant predictors. Finally, the diagnostic performance of the RFS was testified and further validated in another 177 pairs of VAP case-control study.

Results

LASSO, RF and XGBoost consistently revealed significant associations of length of stay before MV, MV time, surgery, tracheotomy, multiple drug resistant organism infection, C-reactive protein, PaO2, and APACHE II score with VAP. RFS was significantly linearly associated with VAP risk [odds ratio and 95 % confidence interval = 2.699 (2.347, 3.135)], and showed good discriminations for VAP both in discovery stage [area under the curve (AUC) = 0.857] and validation stage (AUC = 0.879).

Conclusions

Results of this study revealed co-occurrence of multiple predictors for VAP risk. The risk factor scoring system proposed is a potentially useful predictive tool for clinical targets for VAP prevention.
背景:呼吸机相关肺炎(VAP)是重症监护病房中需要机械通气(MV)的患者中最重要的医院获得性感染之一,但预防VAP的有效且可靠的可预测工具却相对缺乏:本研究旨在建立一个加权风险评分系统,以检测两阶段 VAP 病例对照研究中的 VAP 风险,并评估风险因素评分(RFS)对 VAP 的诊断性能。我们通过最小绝对收缩和选择算子(LASSO)、随机森林(RF)和极端梯度提升(XGBoost)模型构建了363例患者和363例对照的预测模型,并根据重要的预测因子计算了加权RFS。最后,在另外 177 对 VAP 病例对照研究中检验并进一步验证了 RFS 的诊断性能:结果:LASSO、RF 和 XGBoost 一致显示,中风前住院时间、中风时间、手术、气管切开、多重耐药菌感染、C 反应蛋白、PaO2 和 APACHE II 评分与 VAP 存在显著相关性。RFS与VAP风险呈明显线性相关[几率和95%置信区间=2.699 (2.347, 3.135)],并且在发现阶段[曲线下面积(AUC)=0.857]和验证阶段(AUC=0.879)对VAP显示出良好的判别能力:本研究结果表明,VAP 风险存在多种预测因素。本研究的结果表明,VAP 风险的多个预测因素同时存在。所提出的风险因素评分系统可能是一种有用的预测工具,可用于预防 VAP 的临床目标。
{"title":"Prediction model, risk factor score and ventilator-associated pneumonia: A two-stage case-control study","authors":"Hua Meng ,&nbsp;Yuxin Shi ,&nbsp;Kaming Xue ,&nbsp;Di Liu ,&nbsp;Xiongjing Cao ,&nbsp;Yanyan Wu ,&nbsp;Yunzhou Fan ,&nbsp;Fang Gao ,&nbsp;Ming Zhu ,&nbsp;Lijuan Xiong","doi":"10.1016/j.jmii.2024.11.005","DOIUrl":"10.1016/j.jmii.2024.11.005","url":null,"abstract":"<div><h3>Background</h3><div>Ventilator-associated pneumonia (VAP) is one of the most important hospital acquired infections in patients requiring mechanical ventilation (MV) in the intensive care unit, but the effective and robust predictable tools for VAP prevention were relatively lacked.</div></div><div><h3>Methods</h3><div>This study aimed to establish a weighted risk scoring system to examine VAP risk among a two-stage VAP case-control study, and to evaluate the diagnostic performance of risk factor score (RFS) for VAP. We constructed a prediction model by least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (XGBoost) models in 363 patients and 363 controls, and weighted RFS was calculated based on significant predictors. Finally, the diagnostic performance of the RFS was testified and further validated in another 177 pairs of VAP case-control study.</div></div><div><h3>Results</h3><div>LASSO, RF and XGBoost consistently revealed significant associations of length of stay before MV, MV time, surgery, tracheotomy, multiple drug resistant organism infection, C-reactive protein, PaO<sub>2</sub>, and APACHE II score with VAP. RFS was significantly linearly associated with VAP risk [odds ratio and 95 % confidence interval = 2.699 (2.347, 3.135)], and showed good discriminations for VAP both in discovery stage [area under the curve (AUC) = 0.857] and validation stage (AUC = 0.879).</div></div><div><h3>Conclusions</h3><div>Results of this study revealed co-occurrence of multiple predictors for VAP risk. The risk factor scoring system proposed is a potentially useful predictive tool for clinical targets for VAP prevention.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"58 1","pages":"Pages 94-102"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cigarette smoke compromises macrophage innate sensing in response to pneumococcal infection 香烟烟雾会损害巨噬细胞对肺炎球菌感染的先天感应。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.10.001
Wei-Chih Liao , Chia-Huei Chou , Mao-Wang Ho , Jo-Tsen Chen , Shu-Ling Chou , Yu-Tsen Huang , Ngoc-Niem Bui , Hui-Yu Wu , Chi-Fan Lee , Wei-Chien Huang , Chih-Ho Lai

Background

Cigarette smoking remains a leading cause of mortality worldwide. Streptococcus pneumoniae, also known as pneumococcus, is one of the most common pathogens that colonizes the human respiratory tract, causing life-threatening infections. Several studies have reported that cigarette smoke (CS) exposure promotes pneumococcal infectivity; however, the underlying mechanisms remain to be illustrated.

Methods

In this study, we prepared cigarette smoke extract (CSE) from tobacco containing nicotine (0.8 mg/cigarette) and tar (10 mg/cigarette) to investigate the effects of CSE on innate immune response using murine macrophage models.

Results

The results from the cytokine array showed that the production of C-C Motif Chemokine Ligand 2 (CCL2), CCL4, CCL3, C-X-C Motif Chemokine Ligand 2 (CXCL2), and CXCL-10, in pneumococcus-infected cells was reduced upon 5 % CSE treatment. Our results further demonstrated that 5 % CSE exposure, followed by pneumococcal challenge, significantly decreased CCL2 and type I interferon (IFN) production in macrophages by inhibiting nuclear factor (NF)-κB and IFN regulatory factor 3 (IRF3) signaling pathways. Moreover, CSE disrupts macrophage polarization and impedes innate immune signaling to suppress pneumococcal phagocytosis by macrophages.

Conclusion

Our results provide evidence that CS manipulates the signaling molecules to subvert macrophage functions, thereby hindering the innate response against pneumococcal infection.
背景:吸烟仍然是导致全球死亡的主要原因。肺炎链球菌又称肺炎球菌,是人类呼吸道中最常见的病原体之一,可引起危及生命的感染。有几项研究报告称,接触香烟烟雾(CS)会促进肺炎球菌的感染性;然而,其根本机制仍有待说明:在这项研究中,我们从含有尼古丁(0.8 毫克/支)和焦油(10 毫克/支)的烟草中制备了香烟烟雾提取物(CSE),并利用小鼠巨噬细胞模型研究了 CSE 对先天性免疫反应的影响:细胞因子阵列的结果表明,5 % CSE 处理后,肺炎球菌感染细胞中 C-C Motif Chemokine Ligand 2 (CCL2)、CCL4、CCL3、C-X-C Motif Chemokine Ligand 2 (CXCL2) 和 CXCL-10 的产生量减少。我们的研究结果进一步表明,暴露于 5 % CSE 后再接受肺炎球菌挑战,可通过抑制核因子 (NF)-κB 和 IFN 调节因子 3 (IRF3) 信号通路,显著减少巨噬细胞中的 CCL2 和 I 型干扰素 (IFN) 的产生。此外,CSE 还能破坏巨噬细胞的极化,阻碍先天性免疫信号传导,从而抑制巨噬细胞对肺炎球菌的吞噬作用:结论:我们的研究结果提供了 CS 操纵信号分子以颠覆巨噬细胞功能的证据,从而阻碍了针对肺炎球菌感染的先天性免疫反应。
{"title":"Cigarette smoke compromises macrophage innate sensing in response to pneumococcal infection","authors":"Wei-Chih Liao ,&nbsp;Chia-Huei Chou ,&nbsp;Mao-Wang Ho ,&nbsp;Jo-Tsen Chen ,&nbsp;Shu-Ling Chou ,&nbsp;Yu-Tsen Huang ,&nbsp;Ngoc-Niem Bui ,&nbsp;Hui-Yu Wu ,&nbsp;Chi-Fan Lee ,&nbsp;Wei-Chien Huang ,&nbsp;Chih-Ho Lai","doi":"10.1016/j.jmii.2024.10.001","DOIUrl":"10.1016/j.jmii.2024.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Cigarette smoking remains a leading cause of mortality worldwide. <em>Streptococcus pneumoniae</em>, also known as pneumococcus, is one of the most common pathogens that colonizes the human respiratory tract, causing life-threatening infections. Several studies have reported that cigarette smoke (CS) exposure promotes pneumococcal infectivity; however, the underlying mechanisms remain to be illustrated.</div></div><div><h3>Methods</h3><div>In this study, we prepared cigarette smoke extract (CSE) from tobacco containing nicotine (0.8 mg/cigarette) and tar (10 mg/cigarette) to investigate the effects of CSE on innate immune response using murine macrophage models.</div></div><div><h3>Results</h3><div>The results from the cytokine array showed that the production of C-C Motif Chemokine Ligand 2 (CCL2), CCL4, CCL3, C-X-C Motif Chemokine Ligand 2 (CXCL2), and CXCL-10, in pneumococcus-infected cells was reduced upon 5 % CSE treatment. Our results further demonstrated that 5 % CSE exposure, followed by pneumococcal challenge, significantly decreased CCL2 and type I interferon (IFN) production in macrophages by inhibiting nuclear factor (NF)-κB and IFN regulatory factor 3 (IRF3) signaling pathways. Moreover, CSE disrupts macrophage polarization and impedes innate immune signaling to suppress pneumococcal phagocytosis by macrophages.</div></div><div><h3><strong>Conclusion</strong></h3><div>Our results provide evidence that CS manipulates the signaling molecules to subvert macrophage functions, thereby hindering the innate response against pneumococcal infection.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"58 1","pages":"Pages 120-127"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling unique effector function-related bulk antibody profiles in long-term hemodialysis patients following COVID-19 mRNA booster vaccination 揭示长期血液透析患者接种 COVID-19 mRNA 强化疫苗后独特的效应功能相关批量抗体概况。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.09.007
Chia-Yi Chou , Chung-Yi Cheng , Chih-Hsin Lee , Makoto Kuro-O , Tso-Hsiao Chen , San-Yuan Wang , Yung-Kun Chuang , Yun-Jung Yang , Yun-Hsuan Lin , I-Lin Tsai

Background

Hemodialysis patients exhibit a reduced response to vaccination and have different vaccine dose regimens. Vaccines induce antibodies and affect the inflammatory balance through antibody glycosylation and effector functions. Therefore, we aimed to analyze the antibody glycosylation profiles in hemodialysis patients who were vaccinated against severe acute respiratory syndrome coronavirus 2, infected with the virus, or both, and compare them with those of dialysis patients in a control group.

Methods

Plasma samples from 112 hemodialysis patients were assigned to four groups: control, infected, vaccinated, and post-vaccine-infected. Paired plasma samples from 47 people with vaccination (vaccinees) were analyzed before and after the booster dose. The same analytical approach was applied to the four groups for a cross-sectional comparison.

Results

Our study found that both vaccination and infection groups showed decreased fucosylation of IgG1, which is associated with a proinflammatory biosignature. However, vaccination also leads to increased galactosylation and bisection of IgG antibodies, which are associated with anti-inflammatory effects and the additional regulation of immune responses. In contrast, infection led to an additional decrease in the fucosylation of IgG2 and IgA, demonstrating a more intense proinflammatory biosignature than vaccination.

Conclusions

Our findings emphasize the proinflammatory biosignature of afucosylation in both vaccination and infection groups. Additionally, we uncovered further regulated profiles related to galactosylation in vaccinees. These findings suggest that antibody investigation for vaccination or infection should not solely focus on neutralization but should also consider effector function-related glycosylation profiling. This comprehensive information can be valuable for fine-tuning vaccine development in the future.
背景:血液透析患者对疫苗接种的反应减弱,疫苗剂量方案也不同。疫苗会诱导抗体,并通过抗体糖基化和效应器功能影响炎症平衡。因此,我们旨在分析接种过严重急性呼吸道综合征冠状病毒 2 疫苗、感染过该病毒或两者兼有的血液透析患者的抗体糖基化谱,并与对照组透析患者的抗体糖基化谱进行比较:将 112 名血液透析患者的血浆样本分为四组:对照组、感染组、接种组和接种后感染组。对接种疫苗的 47 人(接种者)在加强剂量前后的配对血浆样本进行了分析。对四个组别采用相同的分析方法进行横向比较:我们的研究发现,接种组和感染组的 IgG1 肌糖基化都有所下降,而这与促炎生物标志有关。然而,接种疫苗也会导致 IgG 抗体的半乳糖基化和双链化增加,这与抗炎作用和免疫反应的额外调节有关。相比之下,感染导致 IgG2 和 IgA 的岩藻糖基化进一步降低,显示出比接种疫苗更强烈的促炎生物特征:我们的研究结果表明,疫苗接种组和感染组中的岩藻糖基化都具有促炎症生物特征。此外,我们还发现了疫苗接种者中与半乳糖基化相关的进一步调控特征。这些发现表明,针对疫苗接种或感染的抗体调查不应只关注中和作用,还应考虑与效应器功能相关的糖基化谱分析。这些全面的信息对未来疫苗开发的微调很有价值。
{"title":"Unveiling unique effector function-related bulk antibody profiles in long-term hemodialysis patients following COVID-19 mRNA booster vaccination","authors":"Chia-Yi Chou ,&nbsp;Chung-Yi Cheng ,&nbsp;Chih-Hsin Lee ,&nbsp;Makoto Kuro-O ,&nbsp;Tso-Hsiao Chen ,&nbsp;San-Yuan Wang ,&nbsp;Yung-Kun Chuang ,&nbsp;Yun-Jung Yang ,&nbsp;Yun-Hsuan Lin ,&nbsp;I-Lin Tsai","doi":"10.1016/j.jmii.2024.09.007","DOIUrl":"10.1016/j.jmii.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>Hemodialysis patients exhibit a reduced response to vaccination and have different vaccine dose regimens. Vaccines induce antibodies and affect the inflammatory balance through antibody glycosylation and effector functions. Therefore, we aimed to analyze the antibody glycosylation profiles in hemodialysis patients who were vaccinated against severe acute respiratory syndrome coronavirus 2, infected with the virus, or both, and compare them with those of dialysis patients in a control group.</div></div><div><h3>Methods</h3><div>Plasma samples from 112 hemodialysis patients were assigned to four groups: control, infected, vaccinated, and post-vaccine-infected. Paired plasma samples from 47 people with vaccination (vaccinees) were analyzed before and after the booster dose. The same analytical approach was applied to the four groups for a cross-sectional comparison.</div></div><div><h3>Results</h3><div>Our study found that both vaccination and infection groups showed decreased fucosylation of IgG1, which is associated with a proinflammatory biosignature. However, vaccination also leads to increased galactosylation and bisection of IgG antibodies, which are associated with anti-inflammatory effects and the additional regulation of immune responses. In contrast, infection led to an additional decrease in the fucosylation of IgG2 and IgA, demonstrating a more intense proinflammatory biosignature than vaccination.</div></div><div><h3>Conclusions</h3><div>Our findings emphasize the proinflammatory biosignature of afucosylation in both vaccination and infection groups. Additionally, we uncovered further regulated profiles related to galactosylation in vaccinees. These findings suggest that antibody investigation for vaccination or infection should not solely focus on neutralization but should also consider effector function-related glycosylation profiling. This comprehensive information can be valuable for fine-tuning vaccine development in the future.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"58 1","pages":"Pages 27-37"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative monocyte and T cell responses in DENV-exposed subjects from South-East Asia and DENV-naïve residents in Taiwan 东南亚受 DENV 感染者与台湾未感染 DENV 居民的单核细胞和 T 细胞反应比较。
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.11.006
Sheng-Hsuan Wang , Yun-Erh Chuang , Sia-Seng Tan , Tzu-Chuan Ho , Oscar Guey Chuen Perng , Po-Lin Chen

Background/purpose(s)

Dengue virus (DENV) is one of the most troublesome mosquito-borne infectious viruses in tropical and subtropical zones. People with secondary/multiple DENV infections are at an increased risk of developing severe dengue. Both monocytes and T cells are known to play important roles in the immune response against DENV. However, the function of monocytes and T cells in individuals with potentially multiple exposures to DENV is rarely reported.

Method

In the present study, we performed a functional analysis of monocytes and T cells from people with previous DENV infection and DENV-naïve people that stimulated with DENV2 ex vivo.

Results

Our preliminary analysis indicated that the response of monocytes and T cells to DENV2 restimulation was comparable between DENV-exposed and DENV-naïve individuals. Furthermore, the cytokine expression profiles in monocytes from both naïve individuals and previously DENV-exposed subjects were similar after DENV2 stimulation. In addition, it was observed that the function of T cells was also equivalent when monocytes were present as antigen-presenting cells for dengue antigen, NS3, in terms of cell proliferation, interferon-gamma (IFNγ) secretion, and memory response.

Conclusions

Based on the results, it was observed that previously DENV-exposed monocytes and T cells seemed to be anergic during DENV reinfection. However, whether the impaired response of monocytes and T cells against DENV in people with a history of previous DENV infection leads to severe dengue upon secondary infection in endemic areas requires further investigation.
背景/目的:登革热病毒(DENV)是热带和亚热带地区最棘手的蚊媒传染性病毒之一。二次/多次感染 DENV 的人罹患严重登革热的风险会增加。众所周知,单核细胞和 T 细胞在针对 DENV 的免疫反应中发挥着重要作用。然而,关于单核细胞和T细胞在可能多次暴露于登革热病毒的个体中的功能却鲜有报道:在本研究中,我们对既往感染过DENV的人和对DENV不敏感的人的单核细胞和T细胞进行了体外DENV2刺激的功能分析:我们的初步分析表明,DENV暴露者和DENV免疫者的单核细胞和T细胞对DENV2再刺激的反应相当。此外,在DENV2刺激后,未感染DENV的人和以前感染过DENV的人的单核细胞的细胞因子表达谱相似。此外,还观察到当单核细胞作为登革热抗原 NS3 的抗原递呈细胞时,T 细胞在细胞增殖、γ 干扰素(IFNγ)分泌和记忆反应方面的功能也是相同的:根据研究结果,可以观察到先前暴露于登革热病毒的单核细胞和 T 细胞在登革热病毒再感染期间似乎是过敏的。然而,在登革热流行地区,既往有登革热病毒感染史的人的单核细胞和T细胞对登革热病毒的反应受损是否会导致二次感染时出现严重的登革热,还需要进一步研究。
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引用次数: 0
Increased risk of Pneumocystis jirovecii colonization in rheumatoid arthritis patients on biologics and Janus kinase inhibitor 使用生物制剂和 Janus 激酶抑制剂的类风湿性关节炎患者感染肺孢子菌的风险增加
IF 4.5 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jmii.2024.08.013
Ya-Chun Huang , Nan-Yao Lee , Meng-Yu Weng

Background

The prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi).

Methods

A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization.

Results

One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization.

Conclusion

RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o.
风湿病患者中肺孢子虫肺炎(PJ)的发病率正在上升。PJ 定植是传播的蓄水池,并先于 PJ 肺炎的发生。我们旨在阐明类风湿性关节炎(RA)患者在接受生物制剂或 Janus 激酶抑制剂(JAKi)治疗时 PJ 定植的相关性。
{"title":"Increased risk of Pneumocystis jirovecii colonization in rheumatoid arthritis patients on biologics and Janus kinase inhibitor","authors":"Ya-Chun Huang ,&nbsp;Nan-Yao Lee ,&nbsp;Meng-Yu Weng","doi":"10.1016/j.jmii.2024.08.013","DOIUrl":"10.1016/j.jmii.2024.08.013","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of <em>Pneumocystis jirovecii</em> (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi).</div></div><div><h3>Methods</h3><div>A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization.</div></div><div><h3>Results</h3><div>One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration &gt;3 years and age &gt;60 y/o are risk factors for PJ colonization.</div></div><div><h3>Conclusion</h3><div>RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of <em>P. jirovecii</em> colonization. Risk factors of PJ colonization are medication duration &gt;3 years and age &gt; 60 y/o.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"58 1","pages":"Pages 112-119"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Microbiology Immunology and Infection
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