Hang Liu, Mengyao Ma, Xinhao Jia, Mengwei Qian, Bo Pang, Muzi Li, Honglei Zhang, Shijie Ma, Lanlan Zheng
{"title":"TGEV nonstructural protein ORF3b upregulates the expression of SLA-DR at the transcriptional level in monocyte-derived porcine dendritic cells.","authors":"Hang Liu, Mengyao Ma, Xinhao Jia, Mengwei Qian, Bo Pang, Muzi Li, Honglei Zhang, Shijie Ma, Lanlan Zheng","doi":"10.1016/j.micinf.2024.105437","DOIUrl":"10.1016/j.micinf.2024.105437","url":null,"abstract":"<p><p>Transmissible gastroenteritis virus (TGEV) is a porcine intestinal pathogenic coronavirus that can cause acute intestinal diseases in pigs, especially in suckling piglets under two weeks of age, with a mortality rate of 100 %. Dendritic cells (DCs) are important antigen-presenting cells (APCs) that are essential for the initiation and modulation of immune responses in animals. In this study, we used monocyte-derived porcine DCs as an in vitro model of APCs to further study the pathogenic mechanism of TGEV. Our results demonstrated that TGEV successfully replicates in monocyte-derived porcine DCs, whereas UV-inactivated TGEV failed to infect these cells. Importantly, TGEV infection of DCs led to significant upregulation of swine leukocyte antigen II DR (SLA-DR), a key molecule in the major histocompatibility complex class II (MHC-II) family. We further demonstrated that the ORF3b nonstructural protein of TGEV significantly enhances SLA-DR expression at the transcriptional level in porcine DCs. This study provides new insights into the pathogenic mechanisms of TGEV.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105437"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dener Lucas Araújo Dos Santos, Juliana Santana de Curcio, Evandro Novaes, Célia Maria de Almeida Soares
{"title":"miRNAs regulate the metabolic adaptation of Paracoccidioides brasiliensis during copper deprivation.","authors":"Dener Lucas Araújo Dos Santos, Juliana Santana de Curcio, Evandro Novaes, Célia Maria de Almeida Soares","doi":"10.1016/j.micinf.2024.105435","DOIUrl":"10.1016/j.micinf.2024.105435","url":null,"abstract":"<p><p>Copper is an essential metal for cellular processes such as detoxification of reactive oxygen species, oxidative phosphorylation, and iron uptake. However, during infection, the host restricts the bioavailability of this micronutrient to the pathogen as a strategy to combat infection. Recently, we have shown the involvement of miRNAs as an adaptive strategy of P. brasiliensis upon metal deprivation such as iron and zinc. However, their role in copper limitation still needs to be elucidated. Our objective was to characterize the expression profile of miRNAs regulated during copper deprivation in P. brasiliensis and the putative altered processes. Through RNAseq analysis and bioinformatics, we identified 14 differentially expressed miRNAs, two of which putatively regulated oxidative stress response, beta-oxidation, glyoxylate cycle, and cell wall remodeling. Our results suggest that metabolic adaptations carried out by P. brasiliensis in copper deprivation are regulated by miRNAs.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105435"},"PeriodicalIF":2.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgina Nyawo, Charissa C Naidoo, Benjamin G Wu, Benjamin Kwok, Jose C Clemente, Yonghua Li, Stephanie Minnies, Byron Reeve, Suventha Moodley, Thadathilankal-Jess John, Sumanth Karamchand, Shivani Singh, Alfonso Pecararo, Anton Doubell, Charles Kyriakakis, Robin Warren, Leopoldo N Segal, Grant Theron
{"title":"Bad company? The pericardium microbiome in people investigated for tuberculous pericarditis in an HIV-prevalent setting.","authors":"Georgina Nyawo, Charissa C Naidoo, Benjamin G Wu, Benjamin Kwok, Jose C Clemente, Yonghua Li, Stephanie Minnies, Byron Reeve, Suventha Moodley, Thadathilankal-Jess John, Sumanth Karamchand, Shivani Singh, Alfonso Pecararo, Anton Doubell, Charles Kyriakakis, Robin Warren, Leopoldo N Segal, Grant Theron","doi":"10.1016/j.micinf.2024.105434","DOIUrl":"10.1016/j.micinf.2024.105434","url":null,"abstract":"<p><strong>Background: </strong>The site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome.</p><p><strong>Methods: </strong>People with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement.</p><p><strong>Results: </strong>Pericardial fluid microbiota differed in β-diversity among people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis. dTBs were Mycobacterium-, Lacticigenium-, and Kocuria-enriched vs. nTBs. HIV-positive dTBs were Mycobacterium-, Bifidobacterium-, Methylobacterium-, and Leptothrix-enriched vs. HIV-negative dTBs. HIV-positive dTBs on ART were Mycobacterium- and Bifidobacterium-depleted vs. those not on ART. dTBs exhibited enrichment in short-chain fatty acid (SCFA) and mycobacterial metabolism pathways vs. nTBs. Additional non-pericardial involvement (pulmonary infiltrates) was associated with Mycobacterium-enrichment and Streptococcus-depletion. Mycobacterium reads were in 34 % (31/91) of dTBs, 8 % (2/25) of pTBs and 17 % (4/23) nTBs. People with CRP above (vs. below) the median value had different β-diversity (Pseudomonas-depleted). No correlation was found between enriched taxa in dTBs and CRP.</p><p><strong>Conclusions: </strong>Pericardial fluid microbial composition varies by tuberculosis status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance, including mycobacterial reads in nTBs and pTBs, requires evaluation.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105434"},"PeriodicalIF":2.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veronika Pranclova , Lenka Nedvedova , Eliska Kotounova , Vaclav Hönig , Marketa Dvorakova , Marika Davidkova , Tomas Bily , Marie Vancova , Daniel Ruzek , Martin Palus
{"title":"Unraveling the role of human microglia in tick-borne encephalitis virus infection: insights into neuroinflammation and viral pathogenesis","authors":"Veronika Pranclova , Lenka Nedvedova , Eliska Kotounova , Vaclav Hönig , Marketa Dvorakova , Marika Davidkova , Tomas Bily , Marie Vancova , Daniel Ruzek , Martin Palus","doi":"10.1016/j.micinf.2024.105383","DOIUrl":"10.1016/j.micinf.2024.105383","url":null,"abstract":"<div><div>Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus responsible for severe infections of the central nervous system. Although neurons are predominantly targeted, specific involvement of microglia in pathogenesis of TBE is not yet fully understood. In this study, the susceptibility of human microglia to TBEV is investigated, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudörfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. In particular, immune response varied significantly with the viral strain, as shown by the differential secretion of cytokines and chemokines such as IP-10, MCP-1, IL-8 and IL-6, quantified using a Luminex 48-plex assay. The most virulent strain triggered the highest cytokine induction. Electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology and contribute to a deeper understanding of TBE pathogenesis and neuroinflammation.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105383"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos Alcides Nájera , Mercedes Soares-Silva , Fernando Y. Maeda , Wanderson Duarte DaRocha , Isabela Meneghelli , Ana Clara Mendes , Marina Ferreira Batista , Claudio Vieira Silva , José Franco da Silveira , Cristina M. Orikaza , Nobuko Yoshida , Viviane Grazielle Silva , Santuza Maria Ribeiro Teixeira , Daniella Castanheira Bartholomeu , Diana Bahia
{"title":"Trypanosoma cruzi Vps34 colocalizes with Beclin1 and plays a role in parasite invasion of the host cell by modulating the expression of a sub-group of trans-sialidases","authors":"Carlos Alcides Nájera , Mercedes Soares-Silva , Fernando Y. Maeda , Wanderson Duarte DaRocha , Isabela Meneghelli , Ana Clara Mendes , Marina Ferreira Batista , Claudio Vieira Silva , José Franco da Silveira , Cristina M. Orikaza , Nobuko Yoshida , Viviane Grazielle Silva , Santuza Maria Ribeiro Teixeira , Daniella Castanheira Bartholomeu , Diana Bahia","doi":"10.1016/j.micinf.2024.105385","DOIUrl":"10.1016/j.micinf.2024.105385","url":null,"abstract":"<div><div><em>Trypanosoma cruzi</em>, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. <em>T. cruzi</em> gp82 and gp90 are cell surface proteins belonging to Group II <em>trans</em>-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1–Vps34 complexes involved in autophagy and protein sorting. In <em>T. cruzi</em> epimastigotes, (a <em>non</em>-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that <em>T. cruzi</em> Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105385"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luis A. Arteaga-Blanco , Jairo R. Temerozo , Lucas P.S. Tiné , Luíza Dantas-Pereira , Carolina Q. Sacramento , Natalia Fintelman-Rodrigues , Beatriz M. Toja , Suelen Silva Gomes Dias , Caroline S. de Freitas , Camila Couto Espírito-Santo , Ygor P. Silva , Rudimar L. Frozza , Patrícia T. Bozza , Rubem F.S. Menna-Barreto , Thiago Moreno L. Souza , Dumith Chequer Bou-Habib
{"title":"Extracellular vesicles from primary human macrophages stimulated with VIP or PACAP mediate anti-SARS-CoV-2 activities in monocytes through NF-κB signaling pathway","authors":"Luis A. Arteaga-Blanco , Jairo R. Temerozo , Lucas P.S. Tiné , Luíza Dantas-Pereira , Carolina Q. Sacramento , Natalia Fintelman-Rodrigues , Beatriz M. Toja , Suelen Silva Gomes Dias , Caroline S. de Freitas , Camila Couto Espírito-Santo , Ygor P. Silva , Rudimar L. Frozza , Patrícia T. Bozza , Rubem F.S. Menna-Barreto , Thiago Moreno L. Souza , Dumith Chequer Bou-Habib","doi":"10.1016/j.micinf.2024.105400","DOIUrl":"10.1016/j.micinf.2024.105400","url":null,"abstract":"<div><div>Infection by SARS-CoV-2 is associated with uncontrolled inflammatory response during COVID-19 severe disease, in which monocytes are one of the main sources of pro-inflammatory mediators leading to acute respiratory distress syndrome. Extracellular vesicles (EVs) from different cells play important roles during SARS-CoV-2 infection, but investigations describing the involvement of EVs from primary human monocyte-derived macrophages (MDM) on the regulation of this infection are not available. Here, we describe the effects of EVs released by MDM stimulated with the neuropeptides VIP and PACAP on SARS-CoV-2-infected monocytes. MDM-derived EVs were isolated by differential centrifugation of medium collected from cells cultured for 24 h in serum-reduced conditions. Based on morphological properties, we distinguished two subpopulations of MDM-EVs, namely large (LEV) and small EVs (SEV). We found that MDM-derived EVs stimulated with the neuropeptides inhibited SARS-CoV-2 RNA synthesis/replication in monocytes, protected these cells from virus-induced cytopathic effects and reduced the production of pro-inflammatory mediators. In addition, EVs derived from VIP- and PACAP-treated MDM prevented the SARS-CoV-2-induced NF-κB activation. Overall, our findings suggest that MDM-EVs are endowed with immunoregulatory properties that might contribute to the antiviral and anti-inflammatory responses in SARS-CoV-2-infected monocytes and expand our knowledge of EV effects during COVID-19 pathogenesis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105400"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of novel HIV fusion-inhibitory lipopeptides with the M-T hook structure","authors":"Xiuzhu Geng , Xiaohui Ding , Yuanmei Zhu , Huihui Chong , Yuxian He","doi":"10.1016/j.micinf.2024.105366","DOIUrl":"10.1016/j.micinf.2024.105366","url":null,"abstract":"<div><div><span><span>Combination antiretroviral therapy (cART) has significantly improved the survival of HIV-infected individuals, but long-term treatment can cause side-effects and drug resistance; thus, the development of new antivirals is of importance. We previously identified an M-T hook structure and accordingly designed short-peptide fusion inhibitor<span><span> 2P23, which mainly targets the gp41<span> pocket site and displays potent, broad-spectrum anti-HIV activity. In this study, we continuingly characterized the amino acid sequences of peptide and lipopeptide-based inhibitors containing the M-T hook residues. Among a group of lipopeptides, </span></span>stearic acid (C18)-modified LP-25 and LP-29 exhibited greatly improved inhibitions against divergent HIV-1 subtypes and drug-resistant mutants. LP-25 and LP-29 were evaluated in </span></span>rhesus macaques, and the </span><em>ex vivo</em> inhibition data demonstrated their potent, long-lasting <em>in vivo</em><span> anti-HIV activity, with LP-25 much better than LP-29. Both the lipopeptides displayed high α-helicity, thermostability<span> and binding ability to a target-mimic peptide, and they were metabolically stable when treated with high temperature, proteolytic enzymes<span><span>, human or monkey sera and human liver microsomes. Therefore, our studies have provided critical information for understanding the structure-activity relationship of HIV fusion inhibitors with the M-T hook structure and offered novel candidates for </span>drug development.</span></span></span></div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105366"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaolong Yao , Yuqing He , Canhe Zhu , Shangmin Yang , Jing Wu , Fei Ma , Ping Jin
{"title":"miR-190 restores the innate immune homeostasis of Drosophila by directly inhibiting Tab2 in Imd pathway","authors":"Xiaolong Yao , Yuqing He , Canhe Zhu , Shangmin Yang , Jing Wu , Fei Ma , Ping Jin","doi":"10.1016/j.micinf.2024.105399","DOIUrl":"10.1016/j.micinf.2024.105399","url":null,"abstract":"<div><div>The <em>Drosophila</em> Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after <em>Escherichia coli</em> infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases <em>Drosophila</em> survival rates upon lethal <em>Enterobacter cloacae</em> infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of <em>Tab2.</em> In addition, the dynamic expression pattern of AMPs (<em>Dpt</em>, <em>AttA</em>, <em>CecA1</em>), <em>miR-190</em> and <em>Tab2</em> in the wild-type flies reveals that miR-190 play an important role in <em>Drosophila</em> immune homeostasis restoration at the late stage of <em>E. coli</em> infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting <em>Tab2</em> and promote immune homeostasis restoration in <em>Drosophila</em> Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105399"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zoja Germuskova , Elisa Sosa , Amaya Campillay Lagos , Hege Vangstein Aamot , Mathew A. Beale , Claire Bertelli , Jonas Björkmann , Natacha Couto , Lena Feige , Gilbert Greub , Erika Tång Hallbäck , Emma B. Hodcroft , Dag Harmsen , Laurent Jacob , Keith A. Jolley , Andre Kahles , Alison E. Mather , Richard A. Neher , Aitana Neves , Stefan Niemann , Adrian Egli
{"title":"Conference report: the first bacterial genome sequencing pan-European network conference","authors":"Zoja Germuskova , Elisa Sosa , Amaya Campillay Lagos , Hege Vangstein Aamot , Mathew A. Beale , Claire Bertelli , Jonas Björkmann , Natacha Couto , Lena Feige , Gilbert Greub , Erika Tång Hallbäck , Emma B. Hodcroft , Dag Harmsen , Laurent Jacob , Keith A. Jolley , Andre Kahles , Alison E. Mather , Richard A. Neher , Aitana Neves , Stefan Niemann , Adrian Egli","doi":"10.1016/j.micinf.2024.105410","DOIUrl":"10.1016/j.micinf.2024.105410","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105410"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}