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SARS-CoV-2 infection in the context of Kawasaki disease and multisystem inflammatory syndrome in children. 儿童川崎病和多系统炎症综合征背景下的SARS-CoV-2感染
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 DOI: 10.1007/s00430-022-00756-3
Barbara Anna Folga, Corrinna Jade Karpenko, Bogna Grygiel-Górniak

Recent studies have noted an increasing number of Kawasaki-like cases in the pediatric population following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the literature, the condition is described as multiple inflammatory syndrome in children (MIS-C) or pediatric inflammatory syndrome (PIMS). A similar clinical course of Kawasaki disease (KD) and MIS-C causes difficulties in distinguishing between both conditions. However, the differential diagnosis is crucial since patients with MIS-C can present severe symptoms (myocardial dysfunction, fever, mucocutaneous symptoms) and require more extensive monitoring during treatment than children diagnosed with KD. Along with assessing epidemiological and genetic factors, it is imperative to estimate the risk of developing MIS-C in KD patients with confirmed SARS-CoV-2 infection. Genetic predispositions, such as the ITPKC gene polymorphism in KD, ACE deletion (D) polymorphism in SARS-CoV-2, and inborn errors of immunity (IEIs) in MIS-C affect the regulation of immune system complex clearances and cellular adaptations. The virus has a tropism for both vascular and respiratory cells, which further causes additional symptoms necessitating standard therapy with antithrombotic treatment. The diagnostic criteria for KD, MIS-C, and SARS-CoV-2 help differentiate each condition and optimize treatment strategies. Unfortunately, long-term outcomes in KD patients who develop MIS-C due to SARS-CoV-2 infection have been inadequately documented due to the timing of the pandemic, further displaying the need for longitudinal studies in these patients. This review underlines the differences in diagnosis and treatment of KD and MIS-C. Overall, children with KD may develop MIS-C in the setting of SARS-CoV-2 infection, but further research is needed to outline specific etiologies, prognostic factors, and diagnoses.

最近的研究表明,在感染严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)后,儿科人群中川崎样病例的数量越来越多。在文献中,这种情况被描述为儿童多发性炎症综合征(MIS-C)或儿科炎症综合征(PIMS)。川崎病(KD)和misc相似的临床病程导致难以区分这两种疾病。然而,鉴别诊断至关重要,因为misc患者可出现严重症状(心肌功能障碍、发热、粘膜皮肤症状),并且在治疗期间需要比诊断为KD的儿童更广泛的监测。在评估流行病学和遗传因素的同时,有必要评估确诊为SARS-CoV-2感染的KD患者发生MIS-C的风险。遗传易感性,如KD中的ITPKC基因多态性,SARS-CoV-2中的ACE缺失(D)多态性,以及MIS-C中的先天性免疫错误(IEIs),都会影响免疫系统复合物清除和细胞适应的调节。该病毒对血管细胞和呼吸细胞都有趋向性,这进一步引起额外的症状,需要抗血栓治疗的标准治疗。KD、MIS-C和SARS-CoV-2的诊断标准有助于区分每种疾病并优化治疗策略。不幸的是,由于大流行的时间,由于SARS-CoV-2感染而发展为MIS-C的KD患者的长期结果没有充分的记录,进一步表明需要对这些患者进行纵向研究。这篇综述强调了KD和MIS-C在诊断和治疗上的差异。总的来说,患有KD的儿童可能在SARS-CoV-2感染的情况下发展为MIS-C,但需要进一步的研究来概述具体的病因、预后因素和诊断。
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引用次数: 4
Reduced neutralization against Delta, Gamma, Mu, and Omicron BA.1 variants of SARS-CoV-2 from previous non-Omicron infection. 对先前非 Omicron 感染的 SARS-CoV-2 的 Delta、Gamma、Mu 和 Omicron BA.1 变体的中和能力降低。
IF 5.5 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 Epub Date: 2022-11-12 DOI: 10.1007/s00430-022-00753-6
Paola Pidal, Jorge Fernández, Constanza Airola, Miguel Araujo, Ana María Menjiba, Héctor San Martín, Nicole Bruneau, Monserrat Balanda, Coral Elgueta, Rodrigo Fasce, María Teresa Valenzuela, Ariel Orellana, Eugenio Ramírez

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein.

了解宿主对相关 SARS-CoV-2 变体的免疫反应对于改进诊断、治疗开发和疫苗至关重要。在此,我们分析了 D614G 感染的医护人员在康复后 6 个月的随访中针对 SARS-CoV-2 D614G、Delta、Gamma、Mu 和 Omicron 变体的中和抗体水平。我们对 76 名患者进行了随访:其中女性占 60.5%,男性占 39.5%。有症状和无症状的患者分别占 96.1%和 3.9%。最常见的症状是头痛、肌痛和咳嗽。65.8%、65.8%和92.1%的感染者在随访2个月、4个月和6个月时D614G变异体的中和抗体呈阳性。26.3%、48.7%和65.8%的患者中和了Delta变体,19.7%、32.9%和52.6%的患者中和了Gamma变体,7.9%、19.7%和44.7%的患者中和了Mu变体,4.0%、9.2%和15.8%的患者中和了Omicron变体。在随访期间观察到对伽马和缪变体的中和率较低,同期检测到对奥米克龙变体的中和率也很低。在随访期间,针对 D614G 和 Delta 变体的中和抗体滴度中值显著增加。针对D614G和Delta变体的中和抗体水平与疾病的严重程度之间存在关联。我们的研究结果表明,由于 S 蛋白中存在许多突变,因此免疫系统无法从 Omicron 变体的中和抗体中逃脱。
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引用次数: 0
Variable detection of Omicron-BA.1 and -BA.2 by SARS-CoV-2 rapid antigen tests. 通过 SARS-CoV-2 快速抗原检测仪检测出的 Omicron-BA.1 和 -BA.2 存在差异。
IF 5.5 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 Epub Date: 2022-11-12 DOI: 10.1007/s00430-022-00752-7
Andreas Osterman, Irina Badell, Christopher Dächert, Nikolas Schneider, Anna-Yasemin Kaufmann, Gamze Naz Öztan, Melanie Huber, Patricia M Späth, Marcel Stern, Hanna Autenrieth, Maximilian Muenchhoff, Alexander Graf, Stefan Krebs, Helmut Blum, Ludwig Czibere, Jürgen Durner, Lars Kaderali, Hanna-Mari Baldauf, Oliver T Keppler

During 2022, the COVID-19 pandemic has been dominated by the variant of concern (VoC) Omicron (B.1.1.529) and its rapidly emerging subvariants, including Omicron-BA.1 and -BA.2. Rapid antigen tests (RATs) are part of national testing strategies to identify SARS-CoV-2 infections on site in a community setting or to support layman's diagnostics at home. We and others have recently demonstrated an impaired RAT detection of infections caused by Omicron-BA.1 compared to Delta. Here, we evaluated the performance of five SARS-CoV-2 RATs in a single-centre laboratory study examining a total of 140 SARS-CoV-2 PCR-positive respiratory swab samples, 70 Omicron-BA.1 and 70 Omicron-BA.2, as well as 52 SARS-CoV-2 PCR-negative swabs collected from March 8th until April 10th, 2022. One test did not meet minimal criteria for specificity. In an assessment of the analytical sensitivity in clinical specimen, the 50% limit of detection (LoD50) ranged from 4.2 × 104 to 9.2 × 105 RNA copies subjected to the RAT for Omicron-BA.1 compared to 1.3 × 105 to 1.5 × 106 for Omicron-BA.2. Overall, intra-assay differences for the detection of Omicron-BA.1-containing and Omicron-BA.2-containing samples were non-significant, while a marked overall heterogeneity among the five RATs was observed. To score positive in these point-of-care tests, up to 22-fold (LoD50) or 68-fold (LoD95) higher viral loads were required for the worst performing compared to the best performing RAT. The rates of true-positive test results for these Omicron subvariant-containing samples in the highest viral load category (Ct values < 25) ranged between 44.7 and 91.1%, while they dropped to 8.7 to 22.7% for samples with intermediate Ct values (25-30). In light of recent reports on the emergence of two novel Omicron-BA.2 subvariants, Omicron-BA.2.75 and BJ.1, awareness must be increased for the overall reduced detection rate and marked differences in RAT performance for these Omicron subvariants.

2022 年期间,COVID-19 大流行主要由关注变异体 Omicron(B.1.1.529)及其迅速出现的亚变异体(包括 Omicron-BA.1 和 -BA.2)引起。快速抗原检测(RAT)是国家检测战略的一部分,用于在社区环境中现场识别 SARS-CoV-2 感染,或支持非专业人员在家中进行诊断。我们和其他人最近证明,与德尔塔相比,RAT 对由 Omicron-BA.1 引起的感染的检测能力减弱。在此,我们在一项单中心实验室研究中评估了五种 SARS-CoV-2 RAT 的性能,共检测了 140 份 SARS-CoV-2 PCR 阳性的呼吸道拭子样本(70 份 Omicron-BA.1 和 70 份 Omicron-BA.2),以及 52 份 SARS-CoV-2 PCR 阴性的拭子样本(采集时间为 2022 年 3 月 8 日至 4 月 10 日)。有一项检测不符合特异性最低标准。在评估临床样本的分析灵敏度时,Omicron-BA.1 的 50%检测限(LoD50)为 4.2 × 104 至 9.2 × 105 RNA 拷贝,而 Omicron-BA.2 为 1.3 × 105 至 1.5 × 106。总体而言,检测含 Omicron-BA.1 和含 Omicron-BA.2 样品的检测方法内部差异并不显著,而五种 RAT 之间存在明显的总体异质性。与性能最好的 RAT 相比,性能最差的 RAT 的病毒载量要高出 22 倍(LoD50)或 68 倍(LoD95),才能在这些护理点检测中获得阳性结果。在病毒载量最高的类别中,这些含有 Omicron 亚变体的样本的检测结果真阳性率(Ct 值
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引用次数: 0
A comparative study of IL-33 and its receptor ST2 in a C57BL/6 J mouse model of pulmonary Cryptococcus neoformans infection. IL-33及其受体ST2在C57BL/ 6j肺新生隐球菌感染小鼠模型中的比较研究
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 DOI: 10.1007/s00430-022-00755-4
Zhengxia Wang, Qiyun Ma, Jingxian Jiang, Xiaofan Yang, Enrui Zhang, Yuan Tao, Huidi Hu, Mao Huang, Ningfei Ji, Mingshun Zhang

It has been reported that IL-33 receptor ST2 deficiency mitigates Cryptococcus neoformans (C. neoformans) pulmonary infection in BALB/c mice. IL-33 may modulate immune responses in ST2-dependent and ST2-independent manners. The host genetic background (i.e., BALB/c, C57BL/6 J) influences immune responses against C. neoformans. In the present study, we aimed to explore the roles of IL-33 and ST2 in pulmonary C. neoformans-infected mice on a C57BL/6 J genetic background. C. neoformans infection increased IL-33 expression in lung tissues. IL-33 deficiency but not ST2 deficiency significantly extended the survival time of C. neoformans-infected mice. In contrast, either IL-33 or ST2 deficiency reduced fungal burdens in lung, spleen and brain tissues from the mice following C. neoformans intratracheal inoculation. Similarly, inflammatory responses in the lung tissues were more pronounced in both the IL-33-/- and ST2-/- infected mice. However, mucus production was decreased in IL-33-/- infected mice alone, and the level of IL-5 in bronchoalveolar lavage fluid (BALF) was substantially decreased in the IL-33-/- infected mice but not ST2-/- infected mice. Moreover, IL-33 deficiency but not ST2 deficiency increased iNOS-positive macrophages. At the early stage of infection, the reduced pulmonary fungal burden in the IL-33-/- and ST2-/- mice was accompanied by increased neutrophil infiltration. Collectively, IL-33 regulated pulmonary C. neoformans infection in an ST2-dependent and ST2-independent manner in C57BL/6 J mice.

据报道,IL-33受体ST2缺乏可减轻BALB/c小鼠的新型隐球菌(c . neoformans)肺部感染。IL-33可能以st2依赖性和st2非依赖性的方式调节免疫反应。宿主遗传背景(即BALB/c、C57BL/6 J)影响对新生梭状菌的免疫应答。在本研究中,我们旨在探讨IL-33和ST2在C57BL/6 J遗传背景下肺新生c感染小鼠中的作用。新生弓形虫感染使肺组织IL-33表达升高。缺乏IL-33而不缺乏ST2可显著延长新C.感染小鼠的存活时间。相比之下,IL-33或ST2缺乏均可减少气管内接种新生c后小鼠肺、脾和脑组织中的真菌负荷。同样,IL-33-/-和ST2-/-感染小鼠的肺组织炎症反应更为明显。然而,IL-33-/-单独感染小鼠的粘液生成减少,IL-33-/-感染小鼠的支气管肺泡灌洗液(BALF)中IL-5水平显著降低,而ST2-/-感染小鼠则没有。此外,IL-33缺乏而ST2缺乏增加了inos阳性巨噬细胞。在感染早期,IL-33-/-和ST2-/-小鼠肺部真菌负荷的减少伴随着中性粒细胞浸润的增加。总的来说,IL-33在C57BL/6 J小鼠中以st2依赖和st2独立的方式调节肺部新生C.感染。
{"title":"A comparative study of IL-33 and its receptor ST2 in a C57BL/6 J mouse model of pulmonary Cryptococcus neoformans infection.","authors":"Zhengxia Wang,&nbsp;Qiyun Ma,&nbsp;Jingxian Jiang,&nbsp;Xiaofan Yang,&nbsp;Enrui Zhang,&nbsp;Yuan Tao,&nbsp;Huidi Hu,&nbsp;Mao Huang,&nbsp;Ningfei Ji,&nbsp;Mingshun Zhang","doi":"10.1007/s00430-022-00755-4","DOIUrl":"https://doi.org/10.1007/s00430-022-00755-4","url":null,"abstract":"<p><p>It has been reported that IL-33 receptor ST2 deficiency mitigates Cryptococcus neoformans (C. neoformans) pulmonary infection in BALB/c mice. IL-33 may modulate immune responses in ST2-dependent and ST2-independent manners. The host genetic background (i.e., BALB/c, C57BL/6 J) influences immune responses against C. neoformans. In the present study, we aimed to explore the roles of IL-33 and ST2 in pulmonary C. neoformans-infected mice on a C57BL/6 J genetic background. C. neoformans infection increased IL-33 expression in lung tissues. IL-33 deficiency but not ST2 deficiency significantly extended the survival time of C. neoformans-infected mice. In contrast, either IL-33 or ST2 deficiency reduced fungal burdens in lung, spleen and brain tissues from the mice following C. neoformans intratracheal inoculation. Similarly, inflammatory responses in the lung tissues were more pronounced in both the IL-33<sup>-/-</sup> and ST2<sup>-/-</sup> infected mice. However, mucus production was decreased in IL-33<sup>-/-</sup> infected mice alone, and the level of IL-5 in bronchoalveolar lavage fluid (BALF) was substantially decreased in the IL-33<sup>-/-</sup> infected mice but not ST2<sup>-/-</sup> infected mice. Moreover, IL-33 deficiency but not ST2 deficiency increased iNOS-positive macrophages. At the early stage of infection, the reduced pulmonary fungal burden in the IL-33<sup>-/-</sup> and ST2<sup>-/-</sup> mice was accompanied by increased neutrophil infiltration. Collectively, IL-33 regulated pulmonary C. neoformans infection in an ST2-dependent and ST2-independent manner in C57BL/6 J mice.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"212 1","pages":"53-63"},"PeriodicalIF":5.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10760492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
In vitro and in vivo therapeutic antileishmanial potential of ellagic acid against Leishmania donovani in murine model. 鞣花酸对小鼠模型多诺瓦利什曼原虫的体内外治疗作用。
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 DOI: 10.1007/s00430-022-00754-5
Poonam Keshav, Deepak Kumar Goyal, Sukhbir Kaur

Parasite of genus Leishmania viz. L. donovani and L. infantum cause visceral leishmaniasis (VL) or Kala-azar, systemic disease with significant enlargement of the liver and spleen, weight loss, anemia, fever and immunosuppression. The silent expansion of vectors, reservoir hosts and resistant strains is also of great concern in VL control. Considering all these issues, the present study focused on in vitro and in vivo antileishmanial screening of ellagic acid (EA) against L. donovani. The in vitro study was performed against the protozoan parasite L. donovani and a 50% inhibitory concentration was calculated. The DNA arrest in the sub-G0/G1 phase of the cell cycle was studied. In vivo studies included the assessment of parasite burden and immunomodulation in response to treatment of ellagic acid in BALB/c mice. The levels of Th1 and Th2 cytokines and isotype antibodies were assessed in different groups of mice. EA showed in vitro parasiticidal activity with IC50 18.55 µg/mL and thwarted cell-cycle progression at the sub-G0/G1 phase. Administration of ellagic acid to the BALB/c mice reported diminution of splenic and hepatic parasite burden coupled with an expansion of CD4+ and CD8+ T lymphocytes. EA further potentiated a protective immune response with augmentation of Th1 type immune response evidenced by elevation of serum IgG2a levels and DTH response. EA was reported to be safe and non-toxic to the THP-1 cell line as well as to the liver and kidneys of mice. These findings endorse the therapeutic potential of EA with significant immunomodulation and can serve as a promising agent against this debilitating parasitic disease.

利什曼原虫属寄生虫,即多诺瓦氏利什曼原虫和婴儿利什曼原虫,可引起内脏利什曼病(VL)或黑热病,这是一种全身性疾病,肝脏和脾脏明显肿大,体重减轻,贫血,发烧和免疫抑制。病媒、宿主和耐药菌株的无声扩展也是VL控制的重要问题。考虑到这些问题,本研究的重点是体外和体内筛选鞣花酸(EA)抗多诺瓦杆菌的利什曼原虫。体外实验对多诺瓦氏L.原虫进行了抑菌实验,计算了50%的抑菌浓度。研究了细胞周期亚g0 /G1期的DNA阻滞。体内研究包括评估BALB/c小鼠体内寄生虫负担和鞣花酸处理后的免疫调节。检测各组小鼠Th1、Th2细胞因子水平及同型抗体水平。EA显示体外杀虫活性,IC50为18.55µg/mL,并在亚g0 /G1期阻碍细胞周期进程。BALB/c小鼠经鞣花酸处理后,脾脏和肝脏寄生虫负担减轻,CD4+和CD8+ T淋巴细胞增加。通过血清IgG2a水平和DTH反应的升高,EA进一步增强了Th1型免疫反应的保护性免疫反应。据报道,EA对THP-1细胞系以及小鼠的肝脏和肾脏是安全无毒的。这些发现支持EA具有显著免疫调节的治疗潜力,可以作为一种有希望的药物来治疗这种使人衰弱的寄生虫病。
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引用次数: 3
IgG antibody response to pneumococcal-conjugated vaccine (Prevenar®13) in children with immunodeficiency disorders. 免疫缺陷疾病儿童对肺炎球菌结合疫苗(Prevenar®13)的IgG抗体反应
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 DOI: 10.1007/s00430-022-00759-0
Marta Garrido-Jareño, José Miguel Sahuquillo-Arce, Héctor Rodríguez-Vega, Carmen Lloret-Sos, Ana Gil-Brusola, José Luis López-Hontangas, María Nuñez-Beltran, Jordi Tortosa-Carreres, José Ángel García-García, Lourdes Cordón, Leonor Puchades-Carrasco, Carmen Carreras-Gil de Santivañes, Antonio Pineda-Lucena, Javier Pemán-García

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented.

测定抗肺炎球菌荚膜多糖(抗pnps) IgG滴度是对疑似免疫缺陷疾病(ID)患者进行免疫学评估的重要工具,可以降低发病率和死亡率,减少严重感染。回顾性地,我们研究了抗pnps IgG对3种剂量的Prevenar®13的应答、免疫系统成分水平、白细胞群和ID儿童临床数据之间的关系。接种疫苗后至少4周采集血清样本。随后进行多血清型酶联免疫吸附试验(ELISA)。87名儿童(12岁以下)报名参加。原发性免疫缺陷障碍(PID)最为常见(45例),其次是可能性免疫缺陷障碍(POID)(19例)、继发性免疫缺陷障碍(SID)(15例)和混合性免疫缺陷障碍(MID)(8例)。中位年龄为3岁(1.50 ~ 5.33)岁,男性占65%。47例(54%)患者检测到抗pnps IgG(滴度≤50 mg/L)产生不足,特别是MID组,所有患者均接受免疫抑制治疗。PCV13应答者白细胞群水平均值较高,CD4 + /CD8 + T淋巴细胞(p = 0.372, p = 0.014)、CD56 + /CD16 + NK细胞(p = 0.016)差异有统计学意义。既往骨髓移植患者对PCV13反应最差。肺炎球菌IgG抗体滴度(接种后)以及临床和分析标记。
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引用次数: 1
Acinetobacter baumannii reinforces the pathogenesis by promoting IL-17 production in a mouse pneumonia model. 在小鼠肺炎模型中,鲍曼不动杆菌通过促进 IL-17 的产生来强化发病机制。
IF 5.5 3区 医学 Q1 IMMUNOLOGY Pub Date : 2023-02-01 Epub Date: 2022-12-03 DOI: 10.1007/s00430-022-00757-2
Yangyang Zhou, Chuanying Xiang, Ning Wang, Xiaomin Zhang, Yu Xie, Hong Yang, Gang Guo, Kaiyun Liu, Yan Li, Yun Shi

Interleukin-17 (IL-17) is involved in host defense against bacterial infection. Little is known about the role of IL-17 in A. baumannii-infected pneumonia. Our objective was to investigate the role of IL-17 in pulmonary A. baumannii infection in a mouse model. We infected C57BL/6 mice intra-tracheally (i.t.) with A. baumannii to establish pneumonia model and found A. baumannii infection elevated IL-17 expression in lungs. IL-17-deficient (Il17-/-) mice were resistant to pulmonary A. baumannii infection, showing improved mice survival, reduced bacteria burdens, and alleviated lung inflammation. Further, treatment of A. baumannii-infected Il17-/- mice with IL-17 exacerbated the severity of pneumonia. These data suggest a pathogenic role of IL-17 in pulmonary A. baumannii infection. Further, the infiltration and phagocytic function of neutrophils in broncho-alveolar lavage fluid were detected by flow cytometry. The results showed that Il17-/- mice had increased neutrophil infiltration and enhanced phagocytosis in neutrophils at the early time of infection. Treatment of mice with IL-17 suppressed phagocytic function of neutrophils. All data suggest that IL-17 promotes susceptibility of mice to pulmonary A. baumannii infection by suppressing neutrophil phagocytosis at early time of infection. Targeting IL-17 might be a potential therapeutic strategy in controlling the outcome of A. baumannii pneumonia.

白细胞介素-17(IL-17)参与宿主对细菌感染的防御。人们对 IL-17 在鲍曼尼菌感染肺炎中的作用知之甚少。我们的目的是在小鼠模型中研究 IL-17 在鲍曼不动杆菌肺部感染中的作用。我们用C57BL/6小鼠气管内感染鲍曼尼菌建立了肺炎模型,发现鲍曼尼菌感染会升高肺中IL-17的表达。IL-17缺失(Il17-/-)小鼠对肺部鲍曼不动杆菌感染有抵抗力,小鼠存活率提高,细菌负担减少,肺部炎症减轻。此外,用 IL-17 处理感染了鲍曼尼氏菌的 Il17-/- 小鼠会加重肺炎的严重程度。这些数据表明,IL-17 在肺部鲍曼不动杆菌感染中具有致病作用。此外,还利用流式细胞术检测了支气管肺泡灌洗液中中性粒细胞的浸润和吞噬功能。结果显示,Il17-/-小鼠在感染早期中性粒细胞浸润增加,吞噬功能增强。用 IL-17 处理小鼠可抑制中性粒细胞的吞噬功能。所有数据都表明,IL-17能在感染早期抑制中性粒细胞的吞噬功能,从而提高小鼠对肺部鲍曼不动杆菌感染的易感性。以IL-17为靶点可能是控制鲍曼尼氏菌肺炎结局的一种潜在治疗策略。
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引用次数: 0
Resistance to fosfomycin is increasing and is significantly associated with extended-spectrum β-lactamase-production in urinary isolates of Escherichia coli. 对磷霉素的耐药性正在增加,并与尿中分离的大肠杆菌的广谱β-内酰胺酶产生显著相关。
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2022-12-01 Epub Date: 2022-09-03 DOI: 10.1007/s00430-022-00749-2
Esther Ríos, María Del Carmen López Diaz, Esther Culebras, Iciar Rodríguez-Avial, Carmen Rodríguez-Avial

Fosfomycin has become a therapeutic option in urinary tract infections. Our objective was to evaluate the in vitro activity of fosfomycin against Escherichia coli isolated from urine samples in 2013, 2018 and 2021. We also determined a putative association between fosfomycin resistance and extended-spectrum β-lactamases (ESBL) production. Fosfomycin activity was evaluated against 7367, 8128 and 5072 Escherichia coli urinary isolates in 2013, 2018 and 2021, respectively. We compare the prevalence of fosfomycin-resistant strains among the ESBL- and non-ESBL-producing isolates. MICs of fosfomycin, cefotaxime, and cefotaxime-clavulanate were determined by a microdilution method. 302 ESBL-producers were selected to determine MICs of fosfomycin by agar dilution and genes encoding ESBLs were detected by PCR. Among the total of ESBL-producing strains, 14.3%, 20.8% and 20% were resistant to fosfomycin in 2013, 2018 and 2021, respectively, whereas fosfomycin resistance in non-ESBL producers was 3.5%, 4.05% and 5.53% for each year (P ≤ 0.001). In the 302 selected ESBL-producing isolates, CTX-M was the main ESBL (228 isolates), being 50.7% CTX-M-15. Resistance to fosfomycin among these ESBL-producing strains was associated (P = 0.049) with isolates that produced the CTX-M type. Our data show that fosfomycin resistance is increasing in Escherichia coli urinary isolates and it is related to ESBL-production. A follow-up of fosfomycin resistance is required.

磷霉素已成为尿路感染的一种治疗选择。我们的目的是评估磷霉素对2013年、2018年和2021年尿液样本中分离的大肠杆菌的体外活性。我们还确定了磷霉素耐药性与广谱β-内酰胺酶(ESBL)产生之间的推定关联。分别于2013年、2018年和2021年对7367、8128和5072株尿分离的大肠杆菌进行磷霉素活性评价。我们比较了产ESBL和非产ESBL分离株中磷霉素耐药菌株的流行情况。采用微量稀释法测定磷霉素、头孢噻肟和头孢噻肟-克拉维酸的mic。选择302个ESBLs生产者,琼脂稀释法测定磷霉素mic, PCR检测ESBLs编码基因。产esbl菌株中,2013年、2018年和2021年对磷霉素耐药率分别为14.3%、20.8%和20%,而非产esbl菌株对磷霉素耐药率分别为3.5%、4.05%和5.53% (P≤0.001)。302株产ESBL的分离株中,CTX-M为主要的ESBL(228株),占50.7%。产esbl菌株对磷霉素的耐药性与产CTX-M型菌株相关(P = 0.049)。我们的数据显示,尿分离的大肠杆菌对磷霉素的耐药性正在增加,这与esbls的产生有关。需要对磷霉素耐药性进行随访。
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引用次数: 4
Low rate of asymptomatic carriage and salivary immunoglobulin A response to Group A Streptococci in the healthy adult population in Finland. 芬兰健康成人对A群链球菌无症状携带和唾液免疫球蛋白A应答率低
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2022-12-01 Epub Date: 2022-09-02 DOI: 10.1007/s00430-022-00750-9
Emilia Lönnqvist, Kirsi Gröndahl-Yli-Hannuksela, Vuokko Loimaranta, Jaana Vuopio

Streptococcus pyogenes, also called group A streptococcus (GAS), is a human pathogen causing a wide range of infections ranging from mild tonsillitis to severe, life threatening conditions such as bacteraemia, necrotizing fasciitis, and streptococcal toxic shock syndrome. GAS may also colonise the oropharynx without causing any signs of disease which is known as asymptomatic carriage. This study aims to investigate IgA responses against GAS and oral streptococci from saliva samples collected from healthy Finnish adults. In addition, asymptomatic throat GAS carriage was studied. The study participants consisted of healthy adult volunteers who provided one saliva sample, a throat swab, and a background questionnaire. Total salivary IgA, and GAS specific IgA were analysed from the saliva samples using enzyme-linked immunosorbent assays (ELISA) and the results were compared to oral streptococci specific IgA levels. Asymptomatic GAS throat carriers were identified by bacterial culture, and the isolates were emm typed. Samples from a total of 182 individuals were analysed. The median salivary IgA concentration was 62.9 µg/ml (range 17.3-649.9 µg/ml), and median GAS and oral streptococcal specific IgA concentrations 2.7 and 3.3 arbitrary units (AU, range 1.4-7.4 AU and 1.6-12.0 AU), respectively. Three individuals with asymptomatic GAS throat carriage were identified.

化脓性链球菌,也被称为A群链球菌(GAS),是一种人类病原体,引起广泛的感染,从轻微的扁桃体炎到严重的危及生命的疾病,如菌血症、坏死性筋膜炎和链球菌中毒性休克综合征。气体也可能在口咽部定殖而不引起任何疾病迹象,称为无症状携带。本研究旨在研究从健康芬兰成年人的唾液样本中采集的IgA对GAS和口腔链球菌的反应。此外,对无症状喉部气体输送进行了研究。研究参与者包括健康的成年志愿者,他们提供了一份唾液样本、一份咽拭子和一份背景调查问卷。采用酶联免疫吸附试验(ELISA)分析唾液样本中的唾液总IgA和GAS特异性IgA,并将结果与口腔链球菌特异性IgA水平进行比较。通过细菌培养鉴定无症状GAS喉部携带者,分离株为emm型。研究人员分析了182人的样本。唾液IgA浓度中位数为62.9µg/ml(范围为17.3 ~ 649.9µg/ml), GAS和口腔链球菌特异性IgA浓度中位数分别为2.7和3.3任意单位(范围为1.4 ~ 7.4 AU和1.6 ~ 12.0 AU)。发现3例无症状气体喉部牵引。
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引用次数: 0
Immunological imbalance in microcephalic children with congenital Zika virus syndrome. 先天性寨卡病毒综合征小头畸形儿童的免疫失调。
IF 5.4 3区 医学 Q1 IMMUNOLOGY Pub Date : 2022-12-01 Epub Date: 2022-07-20 DOI: 10.1007/s00430-022-00746-5
Amanda Costa Ayres Salmeron, Wallace Pitanga Bezerra, Rafaela Lúcia Lopes de Souza, Luanderson Cardoso Pereira, Lícia Maria do Nascimento, Anna Cláudia Calvielli Castelo Branco, Luiza Emilia Cavalcanti Simas, Valéria Azevedo de Almeida, Pedro Henrique de Souza Palmeira, Christiane Medeiros Bezerra, Paulo Marcos Matta Guedes, Maria Notomi Sato, Valéria Soraya de Farias Sales, Reginaldo Antônio de Oliveira Freitas Júnior, Tatjana de Souza Lima Keesen, Manuela Sales Lima Nascimento

Microcephalic children due congenital Zika virus syndrome (CZS) present neurological symptoms already well described. However, several other alterations can also be observed. Here, we aimed to evaluate the immune system of microcephaly CZS children. We showed that these patients have enlarged thymus, spleen and cervical lymph nodes, analysed by ultrasound and compared to the reference values for healthy children. In the periphery, they have an increase in eosinophil count and morphological alterations as hypersegmented neutrophils and atypical lymphocytes, even in the absence of urinary tract infections, parasitological infections or other current symptomatic infections. Microcephalic children due CZS also have high levels of IFN-γ, IL-2, IL-4, IL-5 and type I IFNs, compared to healthy controls. In addition, this population showed a deficient cellular immune memory as demonstrated by the low reactivity to the tuberculin skin test even though they had been vaccinated with BCG less than 2 years before the challenge with the PPD. Together, our data demonstrate for the first time that CZS can cause alterations in primary and secondary lymphoid organs and also alters the morphology and functionality of the immune system cells, which broadens the spectrum of CZS symptoms. This knowledge may assist the development of specific therapeutic and more efficient vaccination schemes for this population of patients.

先天性寨卡病毒综合征(CZS)引起的小头症儿童表现出已经得到很好描述的神经系统症状。然而,也可以观察到其他一些变化。在这里,我们旨在评估小头畸形CZS儿童的免疫系统。我们发现这些患者胸腺、脾脏和颈部淋巴结肿大,通过超声分析并与健康儿童的参考值进行比较。在外周,即使没有尿路感染、寄生虫感染或其他当前有症状的感染,它们也有嗜酸性粒细胞计数增加和形态改变,如超节段性中性粒细胞和非典型淋巴细胞。与健康对照相比,CZS引起的小头症儿童也有高水平的IFN-γ、IL-2、IL-4、IL-5和I型IFN。此外,该人群表现出细胞免疫记忆缺陷,对结核菌素皮肤试验的低反应性证明了这一点,即使他们在PPD挑战前不到2年接种过卡介苗。总之,我们的数据首次表明,cz可引起原发性和继发性淋巴器官的改变,并改变免疫系统细胞的形态和功能,这扩大了cz症状的范围。这一知识可能有助于为这一患者群体制定特定的治疗性和更有效的疫苗接种方案。
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引用次数: 1
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Medical Microbiology and Immunology
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