Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Non-targeted metabolomics and pseudo-targeted lipidomics combined with gut microbes reveal the protective effects of <i>Causonis japonica</i> (Thunb.) Raf. in ulcerative colitis mice.","authors":"Hua Huang, Jie Jiang, Yihua Fan, Xufeng Ding, Fang Li, Chuanxin Liu, Lijiang Ji","doi":"10.3389/fcimb.2024.1397735","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1397735","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammatory tissue damage to the intestinal mucosa and forming intestinal epithelial ulcers. It is one of the most intractable diseases in the world. To date, the mechanism is unclear. <i>Causonis japonica</i> (Thunb.) Raf. (Wu Lianmei in Chinese; WLM), a traditional Chinese medicine, which has a long history as an anti-inflammatory, but its effect on UC was unconfirmed yet. Therefore, we established a dextran sodium sulfate (DSS)-induced UC mice model and evaluated the therapeutic effect of WLM extract. The results indicated that WLM inhibits DSS-induced inflammatory response in colitis <i>in vivo</i>, decrease DSS-induced clinical manifestations, reverses colon length shortening, and reduces tissue damage. The results of ELISA kits suggested that WLM could reverse the levels of DSS-induced inflammatory factors. To explore the mechanism of WLM in treating DSS-induced UC, ¹H NMR and UHPLC-Q/Orbitrap MS were used to perform non-targeted metabolomics analysis; 21 differential metabolites in colon tissues were closely related to UC. Meanwhile, the pseudo-targeted lipidomics based on UHPLC-Q/Trap MS was used to analyze lipid metabolism disorders, and 60 differential lipid compounds were screened. These differential compounds were mainly involved in glycerophospholipid, arachidonic acid, glycerolipid, citric acid, tyrosine, and ether lipid metabolisms. The analysis of gut microbial showed that WLM may improve the symptoms of UC mice by reducing the abundance of <i>Helicobacter</i> and <i>Streptococcus</i> and increasing the abundance of <i>Limosilactobacillus</i> and <i>Akkermansia</i>. Moreover, the real-time qPCR results showed that WLM extract could decrease the mRNA levels of inflammatory factors and may be associated with protecting the integrity of intestinal mucosal barrier by destroying <i>in vivo</i> metabolic pathways, especially by regulating energy and lipid metabolisms and reducing inflammatory reactions. It provides a beneficial reference for studying WLM to elucidate the therapeutic mechanism of UC.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544644","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}

{"title":"ProcCluster® and procaine hydrochloride inhibit the growth of <i>Aspergillus</i> species and exert antimicrobial properties during coinfection with influenza A viruses and <i>A. fumigatus in vitro</i>.","authors":"Sarah König, Josefine Schroeder, Thorsten Heinekamp, Axel A Brakhage, Bettina Löffler, Beatrice Engert, Christina Ehrhardt","doi":"10.3389/fcimb.2024.1445428","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1445428","url":null,"abstract":"<p><strong>Introduction: </strong>Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant <i>Aspergillus</i> strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine.</p><p><strong>Methods: </strong>Conidia of different <i>A. fumigatus</i> strains, <i>A. flavus</i> and <i>A. terreus</i> were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca²⁺ distribution during treatment of <i>A. fumigatus</i> with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during <i>in vitro</i> coinfection of lung epithelial cells with <i>A. fumigatus</i> and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay.</p><p><strong>Results: </strong>Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant <i>A. fumigatus</i> strains. However, the addition of CaCl₂ reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca²⁺ homeostasis. Furthermore, <i>in vitro</i> studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and <i>A. fumigatus</i> during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication.</p><p><strong>Discussion: </strong>This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544646","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}

{"title":"PMCNA_RS00975 activates NF-κB and ERK1/2 through TLR2 and contributes to the virulence of <i>Pasteurella multocida</i>.","authors":"Tenglin Xu, Mingxing Kou, Peili Cao, Benjin Liu, Yating Zheng, Qian Jiang, Jiasen Liu, Hongtao Kang, Mingfa Yang, Dongchun Guo, Liandong Qu","doi":"10.3389/fcimb.2024.1469304","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1469304","url":null,"abstract":"<p><strong>Introduction: </strong><i>Pasteurella multocida</i> is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of <i>P. multocida</i>. Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis.</p><p><strong>Methods: </strong>In this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain <i>C48-1</i> of <i>P. multocida</i>, was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a <i>PMCNA_RS00975</i> gene mutant of <i>P. multocida</i> strain <i>C48-1</i> was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within <i>P. multocida.</i> The recombinant protein PMCNA_RS00975 of <i>P. multocida</i> was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated.</p><p><strong>Results: </strong>The mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of <i>P. multocida.</i> Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages.</p><p><strong>Discussion: </strong>This study identified a novel virulence factor in the <i>C48-1</i> strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against <i>P. multocida.</i></p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544645","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}

{"title":"The influence of perilipin 5 deficiency on gut microbiome profiles in murine metabolic dysfunction-associated fatty liver disease (MAFLD) and MAFLD-hepatocellular carcinoma.","authors":"Marinela Krizanac, Paula Štancl, Paola Berenice Mass-Sanchez, Rosa Karlić, Diana Moeckel, Twan Lammers, Anastasia Asimakopoulos, Ralf Weiskirchen","doi":"10.3389/fcimb.2024.1443654","DOIUrl":"10.3389/fcimb.2024.1443654","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency in <i>Plin5</i> reduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer.</p><p><strong>Methods: </strong>Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and <i>Plin5</i>-deficient (<i>Plin5</i> ^-/-) mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples.</p><p><strong>Results: </strong>Notably, we discovered that the absence of <i>Plin5</i> alone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly, <i>Plin5</i> ^-/- animals exhibited an enrichment of the beneficial taxa <i>Lactobacillus</i> in both animal models.</p><p><strong>Discussion: </strong>Our findings identify <i>Plin5</i> as a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521551","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}

{"title":"Genetic characterization of <i>Neisseria meningitidis</i> isolates recovered from patients with invasive meningococcal disease in Lithuania.","authors":"Anželika Slavinska, Magdalena Kowalczyk, Agnė Kirkliauskienė, Greta Vizuje, Paweł Siedlecki, Joana Bikulčienė, Kristina Tamošiūnienė, Aurelija Petrutienė, Nomeda Kuisiene","doi":"10.3389/fcimb.2024.1432197","DOIUrl":"10.3389/fcimb.2024.1432197","url":null,"abstract":"<p><strong>Introduction: </strong><i>Neisseria meningitidis</i> is a gram-negative bacterium responsible for life-threatening invasive infections known as invasive meningococcal disease and is associated with high fatality rates and serious lifelong disabilities among survivors.</p><p><strong>Methods: </strong>This study aimed to characterize <i>N. meningitidis</i> isolates cultured from blood and cerebrospinal fluid collected between 2009 and 2021 in Lithuania, assess their genomic relationships with European strains, and evaluate the possibility of using a cost-effective method for strain characterization, thus improving the national molecular surveillance of invasive meningococcal disease. In total, 321 <i>N. meningitidis</i> isolates were collected and analyzed using multilocus restriction typing (MLRT). Amplification of the <i>penA</i> gene and restriction fragment length polymorphism analysis were performed to identify the modified <i>penA</i> genes. Based on the MLRT genotyping results, we selected 10 strains for additional analysis using whole-genome sequencing. The sequenced genomes were incorporated into a dataset of publicly available <i>N. meningitidis</i> genomes to evaluate genomic diversity and establish phylogenetic relationships within the Lithuanian and European circulating strains.</p><p><strong>Results: </strong>We identified 83 different strains using MLRT genotyping. Genomic diversity of <i>N. meningitidis</i> genomes analysed revealed 21 different sequence types (STs) circulating in Lithuania. Among these, ST34 was the most prevalent. Notably, three isolates displayed unique combinations of seven housekeeping genes and were identified as novel STs: ST16969, ST16901, and ST16959. The analyzed strains were found to possess virulence factors not commonly found in <i>N. meningitidis</i>. Six distinct <i>penA</i> profiles were identified, each with different frequencies. In the present study, we also identified <i>N. meningitidis</i> strains with new <i>penA</i>, NEIS0123, NEIS1320, NEIS1525, NEIS1600, and NEIS1753 loci variants. In our study, using the cgMLST scheme, Minimum Spanning Tree (MST) analysis did not identify significant geographic relationships between Lithuanian <i>N. meningitidis</i> isolates and strains from Europe.</p><p><strong>Discussion: </strong>Discussion: To our knowledge, this is the first study to employ whole genome sequencing (WGS) method for a comprehensive genetic characterization of invasive <i>N. meningitidis</i> isolates from Lithuania. This approach provides a more detailed and precise analysis of genomic relationships and diversity compared to prior studies relying on traditional molecular typing methods and antigen analysis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521548","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}

{"title":"Natural compound-induced downregulation of antimicrobial resistance and biofilm-linked genes in wastewater <i>Aeromonas</i> species.","authors":"Khristina G Judan Cruz, Okamoto Takumi, Kenneth A Bongulto, Emmanuel E Gandalera, Ngure Kagia, Kozo Watanabe","doi":"10.3389/fcimb.2024.1456700","DOIUrl":"10.3389/fcimb.2024.1456700","url":null,"abstract":"<p><p>Addressing the global antimicrobial resistance (AMR) crisis requires a multifaceted innovative approach to mitigate impacts on public health, healthcare and economic systems. In the complex evolution of AMR, biofilms and the acquisition of antimicrobial resistance genes (ARGs) play a pivotal role. <i>Aeromonas</i> is a major AMR player that often forms biofilm, harbors ARGs and is frequently detected in wastewater. Existing wastewater treatment plants (WWTPs) do not have the capacity to totally eliminate antimicrobial-resistant bacteria favoring the evolution of ARGs in wastewater. Besides facilitating the emergence of AMR, biofilms contribute significantly to biofouling process within the activated sludge of WWTP bioreactors. This paper presents the inhibition of biofilm formation, the expression of biofilm-linked genes and ARGs by phytochemicals andrographolide, docosanol, lanosterol, quercetin, rutin and thymohydroquinone. <i>Aeromonas</i> species were isolated and purified from activated sludge samples. The ARGs were detected in the isolated <i>Aeromonas s</i>pecies through PCR. <i>Aeromonas</i> biofilms were quantified following the application of biocompounds through the microtiter plate assay. qPCR analyses of related genes were done for confirmation. Findings showed that the natural compounds inhibited the formation of biofilms and reduced the expression of genes linked to biofilm production as well as ARGs in wastewater <i>Aeromonas</i>. This indicates the efficacy of these compounds in targeting and controlling both ARGs and biofilm formation, highlighting their potential as innovative solutions for combating antimicrobial resistance and biofouling.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521550","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}

{"title":"Mycobacterium tuberculosis combine with EBV infection in severe adult meningoencephalitis: a rare case reports and literature review.","authors":"Jian Wang, Mengjiao Li, Junchi Zhu, Lijuan Cheng, Ping Kong","doi":"10.3389/fcimb.2024.1361119","DOIUrl":"10.3389/fcimb.2024.1361119","url":null,"abstract":"<p><strong>Background: </strong>Tuberculous meningitis (TBM) with adults Epstein-Barr (EB) virus encephalitis is a very rare infectious disease, with a high mortality and disability. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is highly diagnostic. We report on a case of severe meningoencephalitis caused by co-infection with mycobacterium tuberculosis and EB virus. Brain MRI indicated a parenchyma lesion in the brain. mNGS of CSF indicated Mycobacterium tuberculosis and EB virus amplification, positive serum EB virus IgG antibodies, and improved symptoms after anti-tuberculosis and antiviral treatment. A re-examination of the brain MRI revealed that the significantly absorption of the lesions.</p><p><strong>Case report: </strong>A 49-year-old male patient presented with a chief complaint of headache and fever with consciousness disturbance. The brain magnetic resonance imaging showed a lesions in the right parenchymal brain with uneven enhancement, accompanied by significantly increased intracranial pressure, elevated CSF cell count and protein levels, as well as notably decreased glucose and chloride levels. mNGS of CSF showed the coexistence of Mycobacterium tuberculosis and EBV. The patient was diagnosed as TBM with EBV encephalitis. The patient's symptoms gradually improved with the active administration of anti-tuberculosis combined with antiviral agents, the use of hormones to reduce inflammatory reaction, dehydration to lower intracranial pressure, and intrathecal injection. Subsequent follow-up brain magnetic resonance imaging indicated significant absorption of the lesions, along with a marked decrease in CSF count and protein levels, as well as obvious increase in glucose and chloride levels.</p><p><strong>Conclusion: </strong>TBM associated with adult EBV encephalitis is extremely rare. The disease's early stages are severe and have a high fatality rate. A prompt and accurate diagnosis is particularly important. NGS of CSF is of great value for early diagnosis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521549","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}

{"title":"<i>Trypanosoma cruzi</i>-derived exovesicles contribute to parasite infection, tissue damage, and apoptotic cell death during <i>ex vivo</i> infection of human placental explants.","authors":"Alejandro Fernández-Moya, Bielca Oviedo, Ana Liempi, Jesús Guerrero-Muñoz, Cristian Rivas, Rocío Arregui, Sebastian Araneda, Alberto Cornet-Gomez, Juan Diego Maya, Marioly Müller, Antonio Osuna, Christian Castillo, Ulrike Kemmerling","doi":"10.3389/fcimb.2024.1437339","DOIUrl":"10.3389/fcimb.2024.1437339","url":null,"abstract":"<p><p><i>Trypanosoma cruzi</i>, the causative agent of Chagas disease, can be congenitally transmitted by crossing the placental barrier. This study investigates the role of <i>T. cruzi</i>-derived exovesicles (TcEVs) in facilitating parasite infection and the consequent tissue damage and apoptotic cell death in human placental explants (HPEs). Our findings demonstrate that TcEVs significantly enhance the parasite load and induce tissue damage in HPEs, both in the presence and absence of the parasite. Through histopathological and immunohistochemical analyses, we show that TcEVs alone can disrupt the placental barrier, affecting the basal membrane and villous stroma. The induction of apoptotic cell death is evidenced by DNA fragmentation, caspase 8 and 3, and p18 fragment immunodetection. This damage is exacerbated when TcEVs are combined with <i>T. cruzi</i> infection. These findings suggest that TcEVs play a critical role in the pathogenesis of congenital Chagas disease by disrupting the placental barrier and facilitating parasite transmission to the fetus. This study provides new insights into the mechanisms of transplacental transmission of <i>T. cruzi</i> and highlights the potential of targeting TcEVs as a therapeutic strategy against congenital Chagas disease.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524071","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}

{"title":"<i>Porphyromonas gingivalis</i> triggers microglia activation and neurodegenerative processes through NOX4.","authors":"Anna Magnusson, Rongrong Wu, Isak Demirel","doi":"10.3389/fcimb.2024.1451683","DOIUrl":"10.3389/fcimb.2024.1451683","url":null,"abstract":"<p><p>Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years, attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria <i>Porphyromonas gingivalis</i> and microglia cells and to unravel whether these interactions could contribute to the pathology of Alzheimer's disease. We found, through microarray analysis, that stimulation of microglia cells with <i>P. gingivalis</i> resulted in the upregulation of several Alzheimer's disease-associated genes, including NOX4. We also showed that <i>P. gingivalis</i> lipopolysaccharides (LPS) mediated reactive oxygen species (ROS) production and interleukin 6 (IL-6) and interleukin 8 (IL-8) induction via NOX4 in microglia. The viability of neurons was shown to be reduced by conditioned media from microglia cells stimulated with <i>P. gingivalis</i> LPS and the reduction was NOX4 dependent. The levels of total and phosphorylated tau in neurons were increased by conditioned media from microglia cells stimulated with <i>P. gingivalis</i> or LPS. This increase was NOX4-dependent. In summary, our findings provide us with a potential mechanistic explanation of how the periodontal pathogen <i>P. gingivalis</i> could trigger or exacerbate AD pathogenesis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521547","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}

{"title":"Priming from within: TLR2 dependent but receptor independent activation of the mammary macrophage inflammasome by Streptococcus uberis.","authors":"Abbie Hinds, Philip Ward, Nathan Archer, James Leigh","doi":"10.3389/fcimb.2024.1444178","DOIUrl":"10.3389/fcimb.2024.1444178","url":null,"abstract":"<p><strong>Introduction: </strong><i>Streptococcus uberis</i> is a member of the pyogenic cluster of <i>Streptococcus</i> commonly associated with intramammary infection and mastitis in dairy cattle. It is a poorly controlled globally endemic pathogen responsible for a significant cause of the disease worldwide. The ruminant mammary gland provides an atypical body niche in which immune cell surveillance occurs on both sides of the epithelial tissue. <i>S. uberis</i> does not cause disease in non-ruminant species and is an asymptomatic commensal in other body niches. <i>S. uberis</i> exploits the unusual niche of the mammary gland to initiate an innate response from bovine mammary macrophage (BMMO) present in the secretion (milk) in which it can resist the host immune responses. As a result - and unexpectedly - the host inflammatory response is a key step in the pathogenesis of <i>S.uberis</i>, without which colonisation is impaired. In contrast to other bacteria pathogenic to the bovine mammary gland, <i>S. uberis</i> does not elicit innate responses from epithelial tissues; initial recognition of infection is via macrophages within milk.</p><p><strong>Methods: </strong>We dissected the role of the bacterial protein SUB1154 in the inflammasome pathway using <i>ex vivo</i> bovine mammary macrophages isolated from milk, recombinant protein expression, and a panel of inhibitors, agonists, and antagonists. We combine this with reverse-transcription quantitative real-time PCR to investigate the mechanisms underlying SUB1154-mediated priming of the immune response.</p><p><strong>Results: </strong>Here, we show that SUB1154 is responsible for priming the NLRP3 inflammasome in macrophages found in the mammary gland. Without SUB1154, IL-1β is not produced, and we were able to restore IL-1β responses to a sub1154 deletion <i>S. uberis</i> mutant using recombinant SUB1154. Surprisingly, only by blocking internalisation, or the cytoplasmic TIR domain of TLR2 were we able to block SUB1154-mediated priming.</p><p><strong>Discussion: </strong>Together, our data unifies several contrasting past studies and provides new mechanistic understanding of potential early interactions between pyogenic streptococci and the host.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498154","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}