Medical Microbiology and Immunology最新文献

Inhibiting lipid droplet biogenesis enhances host protection against hypervirulent Klebsiella pneumoniae infections. 抑制脂滴生物生成可增强宿主对高病毒性肺炎克雷伯氏菌感染的保护。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-11-14 DOI: 10.1007/s00430-024-00807-x

Hui-Jung Jung, Hyun Ah Kim, Miri Hyun, Ji Yeon Lee, Young Jae Kim, Seong-Il Suh, Eun-Kyeong Jo, Won-Ki Baek, Jin Kyung Kim

{"title":"Inhibiting lipid droplet biogenesis enhances host protection against hypervirulent Klebsiella pneumoniae infections.","authors":"Hui-Jung Jung, Hyun Ah Kim, Miri Hyun, Ji Yeon Lee, Young Jae Kim, Seong-Il Suh, Eun-Kyeong Jo, Won-Ki Baek, Jin Kyung Kim","doi":"10.1007/s00430-024-00807-x","DOIUrl":"10.1007/s00430-024-00807-x","url":null,"abstract":"Hypervirulent Klebsiella pneumoniae (hvKp), an emerging Kp subtype, has become a serious global pathogen. However, the information regarding host interactions and innate immune responses during hvKp infection is limited. Here, we found that hvKp clinical strains increased triacylglycerol synthesis, resulting in lipid droplets (LDs) formation via the mammalian target of rapamycin signaling pathway in RAW264.7 cells. Treatment with rapamycin, an inhibitor of this pathway, affected LDs formation and antimicrobial responses against clinical hvKp infections. In accordance with the role of LDs in modulating inflammation, the pharmacological inhibition of lipogenesis reduced proinflammatory cytokine expression during hvKp infections. In addition, inhibition of LDs formation using pharmacological inhibitors and knockdown of lipogenesis regulators decreased the intracellular survival of hvKp in macrophages. Moreover, inhibiting LDs biogenesis reduced mortality, weight loss, and bacterial loads in hvKp-infected mice. Collectively, these data suggest that LDs biogenesis is crucial in linking host immune responses to clinical hvKp infections.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"26"},"PeriodicalIF":5.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

MPXV infection impairs IFN response but is partially sensitive to IFN-γ antiviral effect. MPXV 感染会损害 IFN 反应，但对 IFN-γ 的抗病毒作用部分敏感。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-11-11 DOI: 10.1007/s00430-024-00808-w

Licia Bordi, Alessandra D'Auria, Federica Frasca, Valentina Mazzotta, Paola Mazzetti, Matteo Fracella, Gabriella d'Ettorre, Guido Antonelli, Mauro Pistello, Andrea Antinori, Raphael P Viscidi, Fabrizio Maggi, Eleonora Lalle, Carolina Scagnolari

{"title":"MPXV infection impairs IFN response but is partially sensitive to IFN-γ antiviral effect.","authors":"Licia Bordi, Alessandra D'Auria, Federica Frasca, Valentina Mazzotta, Paola Mazzetti, Matteo Fracella, Gabriella d'Ettorre, Guido Antonelli, Mauro Pistello, Andrea Antinori, Raphael P Viscidi, Fabrizio Maggi, Eleonora Lalle, Carolina Scagnolari","doi":"10.1007/s00430-024-00808-w","DOIUrl":"https://doi.org/10.1007/s00430-024-00808-w","url":null,"abstract":"The recent outbreak of monkeypox virus (MPXV) has caused global concern. How the virus evades the interferon (IFN) response is still poorly understood. We analyzed type I/II IFN (IFN-I/II) expression in clinical samples from MPXV-infected patients and measured IFN-I kinetics in MPXV-infected cells. We also evaluated the anti-MPXV activity of IFN-I/II in A549, HeLa and Vero-E6 cell lines. IFN-I/II mRNA expression was detected in skin lesions, anal swabs, nasopharyngeal samples and peripheral blood mononuclear cells (PBMC), with the highest levels in skin lesions (p < 0.05). High MPXV DNA levels in clinical samples were associated with increased IFN-I levels. In vitro, MPXV infection induced a peak of IFN-I between 48 and 72 h post-infection (p < 0.01). Pre-treatment of the A549, HeLa and Vero-E6 cells with high concentrations (≥ 100,000 International Unit, IU/ml) of IFN-α and IFN-ω did not inhibit or had little effect on MPXV replication, while IFN-β moderately reduced MPXV replication by 2.7-1.5 log10 at 100,000 IU/ml. In clinical samples there was a trend for elevated levels of IFN-γ in association with lower MPXV load and in vitro IFN-γ (3,600 IU/ml) strongly reduced viral titers by 3.4-1.6 log10. There were no significant differences in expression of select IFN-stimulated genes (ISGs) in MPXV infection in vitro. This study shows that MPXV delays IFN-I induction and inhibits expression of selected ISGs in vitro and is associated with an IFN-I resistance phenotype in vivo. However, MPXV is less resistant to IFN-γ in vivo and is sensitive to IFN-γ treatment in vitro, suggesting a potential therapeutic role for IFN-γ.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"25"},"PeriodicalIF":5.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623632","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: 0

Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses. 针对 SARS-CoV-2 变体和 SARS 相关冠状病毒设计的双特异性抗体具有更强的广谱性和效力。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-11-09 DOI: 10.1007/s00430-024-00809-9

Fangfang Chang, Qian Wu, Yabin Hu, Zhendong Pan, Yong-Chen Liu, Yue-Zhou Li, Mihnea Bostina, Wenpei Liu, Ping Zhao, Xiaowang Qu, Yi-Ping Li

{"title":"Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses.","authors":"Fangfang Chang, Qian Wu, Yabin Hu, Zhendong Pan, Yong-Chen Liu, Yue-Zhou Li, Mihnea Bostina, Wenpei Liu, Ping Zhao, Xiaowang Qu, Yi-Ping Li","doi":"10.1007/s00430-024-00809-9","DOIUrl":"https://doi.org/10.1007/s00430-024-00809-9","url":null,"abstract":"The concern of COVID-19 persists due to the continuous emergence of variants and the potential spillover of animal coronaviruses. The broad-spectrum neutralizing antibodies play a pivotal role in the prevention and treatment of coronavirus (CoV) infections. Here, we constructed 18 bi-specific antibodies (bsAbs) using 9 antibodies isolated from COVID-19 convalescents and vaccinated individuals, designed as dual variable domain immunoglobulin (DVD-Ig). A bsAb 5-HI showed a high binding capability to the S1 subunit of spike and exhibited breadth and potency against pseudotyped SARS-CoV-2 variants of concerns (VOCs) and SARS-related-CoVs (SARSr-CoVs), with half maximal effective concentration (EC50) of 0.028-3.444 nM and 50% inhibitory concentration (IC50) of 0.008-0.800 nM. In addition, it retained neutralization potency against the peudotyped virus of recently prevalent JN.1 strain (IC50, 12.74 nM). We found that the parental antibodies showed weak or no binding to the receptor binding domain (RBD) of the SARS-CoV, EG.5.1, and JN.1. However, the 5-HI maintained the binding with RBD and prevented the binding between hACE2 and RBD (IC50 for the RBD of SARS-CoV, 1.067 nM; EG.5.1, 0.423 nM; JN.1, 0.223 nM). In neutralization assays with the authentic virus, we found that the 5-HI effectively neutralized Omicron variants XBB.1.5 (IC50, 0.308 nM), EG.5.1 (IC50, 0.129 nM), and JN.1 (IC50, 13.692 nM), while its parental antibodies showed weakened or no neutralization. Therefore, the 5-HI represents a promising candidate for further development in the treatment and prevention of ongoing evolved SARS-CoV-2 VOCs and other SARSr-CoVs that potentially emerge in the future.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"24"},"PeriodicalIF":5.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623624","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: 0

The pathogenic responses elicited during exposure of human intestinal cell line with Giardia duodenalis excretory-secretory products and the potential attributed endocytosis mechanism. 人体肠道细胞系与十二指肠贾第虫排泄-分泌产物接触时引发的致病反应以及潜在的内吞机制。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-10-23 DOI: 10.1007/s00430-024-00806-y

Xiran Yu, Yongwu Yang, Weining Zhu, Min Liu, Jingxue Wu, Steven M Singer, Wei Li

{"title":"The pathogenic responses elicited during exposure of human intestinal cell line with Giardia duodenalis excretory-secretory products and the potential attributed endocytosis mechanism.","authors":"Xiran Yu, Yongwu Yang, Weining Zhu, Min Liu, Jingxue Wu, Steven M Singer, Wei Li","doi":"10.1007/s00430-024-00806-y","DOIUrl":"https://doi.org/10.1007/s00430-024-00806-y","url":null,"abstract":"Giardia duodenalis, an important zoonotic protozoan parasite, adheres to host intestinal epithelial cells (IECs) via the ventral disc and causes giardiasis characterized mainly by diarrhea. To date, it remains elusive how excretory-secretory products (ESPs) of Giardia enter IECs and how the cells respond to the entry. Herein, we initially demonstrated that ESPs evoked IEC endocytosis in vitro. We indicated that ESPs contributed vitally in triggering intrinsic apoptosis, pro-inflammatory responses, tight junction (TJ) protein expressional changes, and autophagy in IECs. Endocytosis was further proven to be implicated in those ESPs-triggered IEC responses. Ten predicted virulent excretory-secretory proteins of G. duodenalis were investigated for their capability to activate clathrin/caveolin-mediated endocytosis (CME/CavME) in IECs. Pyridoxamine 5'-phosphate oxidase (PNPO) was confirmed to be an important contributor. PNPO was subsequently verified as a vital promoter in the induction of giardiasis-related IEC apoptosis, inflammation, and TJ protein downregulation. Most importantly, this process seemed to be involved majorly in PNPO-evoked CME pathway, rather than CavME. Collectively, this study identified Giardia ESPs, notably PNPO, as potentially important pathogenic factors during noninvasive infection. It was also noteworthy that ESPs-evoked endocytosis might play a role in triggering giardiasis-inducing cellular regulation. These findings would deepen our understanding about the role of ESPs, notably PNPO, in the pathogenesis of giardiasis and the potential attributed endocytosis mechanism.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"23"},"PeriodicalIF":5.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503542","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: 0

A plant-based oligomeric CD2v extracellular domain antigen exhibits equivalent immunogenicity to the live attenuated vaccine ASFV-G-∆I177L. 基于植物的低聚物 CD2v 细胞外结构域抗原与减毒活疫苗 ASFV-G-∆I177L 具有相同的免疫原性。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-10-16 DOI: 10.1007/s00430-024-00804-0

Giang Thu Nguyen, Thanh Thi Le, Son Duy Thai Vu, Tra Thi Nguyen, My Thi Tra Le, Van Thi Pham, Hien Thi Thu Nguyen, Thuong Thi Ho, Hang Thi Thu Hoang, Hanh Xuan Tran, Ha Hoang Chu, Ngoc Bich Pham

{"title":"A plant-based oligomeric CD2v extracellular domain antigen exhibits equivalent immunogenicity to the live attenuated vaccine ASFV-G-∆I177L.","authors":"Giang Thu Nguyen, Thanh Thi Le, Son Duy Thai Vu, Tra Thi Nguyen, My Thi Tra Le, Van Thi Pham, Hien Thi Thu Nguyen, Thuong Thi Ho, Hang Thi Thu Hoang, Hanh Xuan Tran, Ha Hoang Chu, Ngoc Bich Pham","doi":"10.1007/s00430-024-00804-0","DOIUrl":"https://doi.org/10.1007/s00430-024-00804-0","url":null,"abstract":"African swine fever (ASF), caused by the African swine fever virus (ASFV), is a deadly, highly contagious disease in both domestic pigs and wild boar. With mortality up to 100%, the disease has been making a serious impact on the swine industry worldwide. Because no effective antiviral treatment has been observed, proactive prevention such as vaccination remains the key to controlling the outbreak. In the pursuit of expediting vaccine development, our current work has made the first report for heterologous production of the viral outer envelope glycoprotein CD2v extracellular domain (CD2v ED), a proposed promising vaccine antigen candidate in the \"green\" synthetic host Nicotiana benthamiana. Protein oligomerization strategies were implemented to increase the immunogenicity of the target antigen. Herein, the protein was expressed in oligomeric forms based on the C-terminally fused GCN4pII trimerization motif and GCN4pII_TP oligomerization motif. Quantitative western blot analysis showed significantly higher expression of trimeric CD2v ED_GCN4pII with a yield of about 12 mg/100 g of fresh weight, in comparison to oligomeric CD2v ED_GCN4pII_TP, revealing the former is the better choice for further studies. The results of purification and size determination by size exclusion chromatography (SEC) illustrated that CD2v ED_GCN4pII was successfully produced in stable oligomeric forms throughout the extraction, purification, and analysis process. Most importantly, purified CD2v ED_GCN4pII was demonstrated to induce both humoral and cellular immunity responses in mice to extents equivalent to those of the live attenuated vaccine ASFV-G-∆I177L, suggesting it as the potential subunit vaccine candidate for preventing ASFV.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"22"},"PeriodicalIF":5.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469514","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: 0

Trivalent outer membrane vesicles-based combination vaccine candidate induces protective immunity against Campylobacter and invasive non-typhoidal Salmonella in adult mice. 基于三价外膜囊泡的候选联合疫苗可诱导成年小鼠对弯曲杆菌和侵袭性非伤寒沙门氏菌产生保护性免疫。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-10-15 DOI: 10.1007/s00430-024-00805-z

Soumalya Banerjee, Prolay Halder, Sanjib Das, Suhrid Maiti, Jeffrey H Withey, Jiro Mitobe, Goutam Chowdhury, Kei Kitahara, Shin-Ichi Miyoshi, Asish Kumar Mukhopadhyay, Shanta Dutta, Hemanta Koley

{"title":"Trivalent outer membrane vesicles-based combination vaccine candidate induces protective immunity against Campylobacter and invasive non-typhoidal Salmonella in adult mice.","authors":"Soumalya Banerjee, Prolay Halder, Sanjib Das, Suhrid Maiti, Jeffrey H Withey, Jiro Mitobe, Goutam Chowdhury, Kei Kitahara, Shin-Ichi Miyoshi, Asish Kumar Mukhopadhyay, Shanta Dutta, Hemanta Koley","doi":"10.1007/s00430-024-00805-z","DOIUrl":"https://doi.org/10.1007/s00430-024-00805-z","url":null,"abstract":"Campylobacter and invasive non-typhoidal Salmonella (iNTS) are among the most common causative agents of gastroenteritis worldwide. As of now, no single combination licensed vaccine is available for public health use against both iNTS and Campylobacter species. Outer-membrane vesicles (OMVs) are nanoscale proteoliposomes released from the surface of gram-negative bacteria during log phase and harbor a variety of immunogenic proteins. Based on epidemiology of infections, we formulated a novel trivalent outer membrane vesicles (TOMVs)-based vaccine candidate against Campylobacter jejuni (CJ), Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE). Isolated OMVs from CJ, ST and SE were combined in equal ratios for formulation of TOMVs and 5 µg of the developed vaccine candidate was used for intraperitoneal immunization of adult BALB/c mice. Immunization with TOMVs significantly activated both the humoral and cellular arm of adaptive immune response. Robust bactericidal effect was elicited by TOMVs immunized adult mice sera. TOMVs immunization induced long-term protective efficacy against CJ, ST and SE infections in mice. The study illustrates the ability of TOMVs-based combination immunogen in eliciting broad-spectrum protective immunity against prevalent Campylobacter and iNTS pathogens. According to the findings, TOMVs can work as a potent combination-based acellular vaccine candidate for amelioration of Campylobacter and iNTS-mediated gastroenteritis.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"21"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469515","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: 0

Cellular immunity to nucleoproteins (NP) of Crimean-Congo hemorrhagic fever virus (CCHFV) and Hazara Virus (HAZV). 对克里米亚-刚果出血热病毒（CCHFV）和哈扎拉病毒（HAZV）核蛋白（NP）的细胞免疫。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-09-25 DOI: 10.1007/s00430-024-00802-2

Merve Kalkan-Yazıcı, Elif Karaaslan, Nesibe Selma Güler-Çetin, Mehmet Z Doymaz

{"title":"Cellular immunity to nucleoproteins (NP) of Crimean-Congo hemorrhagic fever virus (CCHFV) and Hazara Virus (HAZV).","authors":"Merve Kalkan-Yazıcı, Elif Karaaslan, Nesibe Selma Güler-Çetin, Mehmet Z Doymaz","doi":"10.1007/s00430-024-00802-2","DOIUrl":"https://doi.org/10.1007/s00430-024-00802-2","url":null,"abstract":"Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a globally significant vector-borne pathogen with no internationally-licensed preventative and therapeutic interventions. Hazara virus (HAZV), on the other hand, a related Orthonairovirus, has not been reported as a human pathogen. HAZV has been proposed as a surrogate model for studying CCHFV, bisosafety level 4 (BSL-4) agent. Previously, we investigated the humoral immune responses between NPs of these viruses and in this study, we extended the scrutiny to cellular immune responses elicited by NPs of CCHFV and HAZV. Here, mice were immunized with recombinant CCHFV NP and HAZV NP to evaluate the correlates of cell-mediated immunity (CMI). Delayed-type hypersensitivity (DTH) responses were assessed by challenging immunized mice with CCHFV-rNP or HAZV-rNP on the footpad and lymphocyte proliferation assays (LPAs) were performed by stimulating splenocytes in vitro with CCHFV-rNP or HAZV-rNP to compare cellular immune responses. In all test groups, strong DTH and LPA responses were detected against homologous and heterologous challenging antigens. To assess the cytokine response, an RT-qPCR -specific for cytokine mRNAs was utilized. Interestingly, CCHFV NP stimulated groups exhibited a significantly elevated mRNA level of interleukin 17 A (IL-17) compared to HAZV NP, indicating a notable difference in immune responses. This study presents comparison between CMI elicited by NPs of CCHFV and HAZV and contributes to the understanding of a highly pathogenic virus, particularly in the context of the declaration of CCHFV by World Health Organization's (WHO) as a major viral threat to the world.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"20"},"PeriodicalIF":5.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349665","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: 0

Exploration of compounds to inhibit the Panton-Valentine leukocidin of Staphylococcus aureus 抑制金黄色葡萄球菌潘顿-瓦伦丁白细胞介素的化合物探索

IF 5.4 3区医学

Medical Microbiology and Immunology Pub Date : 2024-09-19 DOI: 10.1007/s00430-024-00803-1

Tobias Grebe, Mithra Tatjana Sarkari, Angelika Cherkaoui, Frieder Schaumburg

{"title":"Exploration of compounds to inhibit the Panton-Valentine leukocidin of Staphylococcus aureus","authors":"Tobias Grebe, Mithra Tatjana Sarkari, Angelika Cherkaoui, Frieder Schaumburg","doi":"10.1007/s00430-024-00803-1","DOIUrl":"https://doi.org/10.1007/s00430-024-00803-1","url":null,"abstract":"The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus is associated with necrotizing infections. After binding to complement 5a receptor (C5aR/CD88) and CD45 it causes cytolysis in polymorphonuclear neutrophils (PMNs) as well as inflammasome activation in monocytes. The objective of this study was to test if (ant)agonists of C5aR and CD45 can attenuate the effect of PVL on PMNs and monocytes. We tested the effect of various concentrations of six C5aR (ant)agonists (avacopan, BM213, DF2593A, JPE-1375, PMX205 and W-54011) and one CD45 antagonist (NQ301) to attenuate the cytotoxic effect of PVL on human PMNs and monocytes in vitro. Shifts in the half-maximal effective concentration (EC50) of PVL to achieve a cytotoxic effect on PMNs and modulation of inflammatory cytokine response from monocytes were determined by flow cytometry and IL-1β detection. Pre-treatment of PMNs with avacopan, PMX205 and W-54,011 resulted in 3.6- to 4.3-fold shifts in the EC50 for PVL and were able to suppress IL-1β secretion by human monocytes in the presence of PVL. BM213, DF2593A and NQ301 were unable to change the susceptibility of PMNs towards PVL or reduce inflammasome activation in monocytes. Avacopan, PMX205 and W-54,011 showed protection against PVL-induced cytotoxicity and suppressed IL-1β secretion by monocytes. Clinical studies are needed to prove whether these substances can be used therapeutically as repurposed drugs.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"3 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253942","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: 0

Analytical and clinical evaluation of a novel real-time PCR-based detection kit for Mpox virus. 基于实时 PCR 的新型 Mpox 病毒检测试剂盒的分析和临床评估。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-08-05 DOI: 10.1007/s00430-024-00800-4

Till Bunse, Anne Ziel, Philipp Hagen, George Rigopoulos, Umit Yasar, Hakan Inan, Gurbet Köse, Ulrich Eigner, Rolf Kaiser, Nils Bardeck, Jasmin Köffer, Melissa Kolb, Xiaomei Ren, Deyong Tan, Lizhong Dai, Ulrike Protzer, Jochen M Wettengel

{"title":"Analytical and clinical evaluation of a novel real-time PCR-based detection kit for Mpox virus.","authors":"Till Bunse, Anne Ziel, Philipp Hagen, George Rigopoulos, Umit Yasar, Hakan Inan, Gurbet Köse, Ulrich Eigner, Rolf Kaiser, Nils Bardeck, Jasmin Köffer, Melissa Kolb, Xiaomei Ren, Deyong Tan, Lizhong Dai, Ulrike Protzer, Jochen M Wettengel","doi":"10.1007/s00430-024-00800-4","DOIUrl":"10.1007/s00430-024-00800-4","url":null,"abstract":"Outbreaks of emerging diseases, like Mpox in 2022, pose unprecedented challenges to global healthcare systems. Although Mpox cases globally decreased since the end of 2022, numbers are still significant in the African Region, European Region, Region of the Americas, and Western Pacific Region. Rapid and efficient detection of infected individuals by precise screening assays is crucial for successful containment. In these assays, analytical and clinical performance must be assessed to ensure high quality. However, clinical studies evaluating Mpox virus (MPXV) detection kits using patient-derived samples are scarce. This study evaluated the analytical and clinical performance of a new diagnostic MPXV real-time PCR detection kit (Sansure Monkeypox Virus Nucleic Acid Diagnostic Kit) using patient-derived samples collected in Germany during the MPXV clade IIb outbreak in 2022. Our experimental approach determined the Limit of Detection (LoD) to less than 200 cp/mL using whole blood samples and samples derived from vesicles or pustules. Furthermore, we tested potentially inhibiting substances and pathogens with homologous nucleic acid sequences or similar clinical presentation and detected no cross-reactivity or interference. Following this, the assay was compared to a CE-marked test in a clinical performance study and achieved a diagnostic sensitivity of 100.00% and diagnostic specificity of 96.97%. In summary, the investigated real-time PCR assay demonstrates high analytical performance and concurs with the competitor device with high specificity and sensitivity.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"18"},"PeriodicalIF":5.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Carl Flügge, one of the last holistic hygienists and discoverer of droplet transmission of infectious diseases. 卡尔-弗吕格（Carl Flügge），最后的整体卫生学家之一，传染病飞沫传播的发现者。

IF 5.5 3区医学

Medical Microbiology and Immunology Pub Date : 2024-08-02 DOI: 10.1007/s00430-024-00801-3

Peter R Donald, Stefan H E Kaufmann, Dagmar Schaub, Stephanie Thee, Christoph Lange

{"title":"Carl Flügge, one of the last holistic hygienists and discoverer of droplet transmission of infectious diseases.","authors":"Peter R Donald, Stefan H E Kaufmann, Dagmar Schaub, Stephanie Thee, Christoph Lange","doi":"10.1007/s00430-024-00801-3","DOIUrl":"10.1007/s00430-024-00801-3","url":null,"abstract":"Carl Flügge is best known for the promotion of studies demonstrating the transmission of all manner of infections, but particularly tuberculosis, by coughed droplets. But it is seldom recognised that Flügge was also influential in a number of other fields comprising the practice of hygiene. One-hundred years following his death in 1923, we review literature related to the studies of Flügge and his colleagues and students and illustrate the particular emphasis he laid upon the environment within which disease and its transmission might be fostered or prevented, embracing and studying aspects essential to the health of any community ranging from fundamental microbiology in the laboratory to subjects as disparate as housing, clean water supply, nutrition, sanitation, socio-economic circumstances and climate. Very early in his career he promoted breast feeding for the prevention of seasonal gastro-enteritis and later the sheltering of cough as a means of preventing the transmission of infected respiratory droplets, not only as regards tuberculosis, but also concerning all manner of other respiratory infections. By the time of Flügge's death the complexification of available scientific methodologies comprising hygiene made it difficult for any individual to comprehend and study the wide range of hygiene-related subjects such as Flügge did. Carl Flügge was one of the last holistic hygienists and an originator of the study of environmental health as a pillar of hygiene.","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"213 1","pages":"17"},"PeriodicalIF":5.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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