{"title":"Intranasal Administration of Bivalent RBD Nanoparticles Elicits Strong Systemic Responses That Effectively Block Distal Dissemination of COVID-19.","authors":"Mathurin Seesen, Panya Sunintaboon, Jitra Limthongkul, Yada Janhirun, Hatairat Lerdsamran, Witthawat Wiriyarat, Sukathida Ubol, Tuksin Jearanaiwitayakul","doi":"10.1111/1348-0421.13209","DOIUrl":"https://doi.org/10.1111/1348-0421.13209","url":null,"abstract":"<p><p>The intranasal vaccine against coronavirus disease 2019 (COVID-19) has gained more attention because of its ability to induce both mucosal and systemic immune responses. We have recently developed a c-GAMP-adjuvanted bivalent receptor-binding domain (RBD) vaccine, derived from the ancestral strain and the Omicron variant. We demonstrated here that intranasal administration of this vaccine candidate triggers not only the respiratory but also the systemic immune response against SARS-CoV-2. The immunized mice elicited the broadly neutralizing antibodies against the ancestral strain (Wuhan-1) and variants of concern (Delta, Omicron BA.1, and Omicron BA.5). This route of vaccination also induced potent systemic T cell responses with strong cytotoxic activity against both the Wuhan-1 and Omicron BA.1 strains. Additionally, intranasally immunized mice significantly suppressed SARS-CoV-2 RNA levels in circulation and spleens, indicating effective containment of the virus beyond the respiratory tract. These findings suggest that the intranasal bivalent RBD vaccine holds promise for combating SARS-CoV-2 infections.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586300","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":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13135","DOIUrl":"https://doi.org/10.1111/1348-0421.13135","url":null,"abstract":"<p><b>Cover photograph</b>: Heatmaps of correlations between different mediators in serum of etiological groups. <i>Microbiol Immunol: 69:174-181</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 3","pages":"i-ii"},"PeriodicalIF":1.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530113","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}
{"title":"An Atypical Kappa-Class Chaperone-Usher Fimbriae of a Human Enterotoxigenic Escherichia coli Strain Shows Multi-Host Adherence and Distinct Phylogenetic Feature.","authors":"Hiharu Inoue, Yoshihiko Tanimoto, Dongming Zheng, Erika Ban-Furukawa, Miyoko Inoue, Yuko Omori, Yoshihiro Yamaguchi, Taro Tachibana, Hisashi Aso, Weiping Zhang, Eriko Kage-Nakadai, Yoshikazu Nishikawa, Takayuki Wada","doi":"10.1111/1348-0421.13208","DOIUrl":"https://doi.org/10.1111/1348-0421.13208","url":null,"abstract":"<p><p>The pathogenesis of enterotoxigenic Escherichia coli (ETEC) involves the colonization of hosts by colonization factors (CFs) and the secretion of enterotoxins. CFs, especially chaperone-usher fimbriae, mediate bacterial adhesion to host cells, with extensive genetic diversity observed among isolates. One ETEC strain, O169YN10, possessed a unique plasmid (pEntYN10) encoding three CFs, CS6, and two novel homologs of CS8 and F4 (CS6<sub>O169</sub>, CS8<sub>O169</sub>, and F4<sub>O169</sub>). In this study, F4<sub>O169</sub> was found to play a major role in adhesion to multiple hosts, including human, bovine, and porcine epithelial cells, whereas the other two CSs were less functional. Inhibition assays using antibodies showed that FayG1, one of the two major paralogous adhesins of F4<sub>O169</sub>, directly contributes to human cell adhesion. Despite the established function of FayG1, the FayG2 protein was not detected under the in vitro conditions. Comparative genomics revealed that FayG1 and FayG2 share low homology with other E. coli strains isolated from hosts, suggesting sporadic emergence from an unknown origin.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537405","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":"Analysis of the Functional Role of TIMM29 in the Hepatitis B Virus Life Cycle","authors":"Limia Abueldahab, Yadarat Suwanmanee, Nelly Muriungi, Eriko Ohsaki, Masami Wada, Shihoko Kimura-Ohba, Keiji Ueda","doi":"10.1111/1348-0421.13206","DOIUrl":"10.1111/1348-0421.13206","url":null,"abstract":"<p>Hepatitis B virus (HBV) causes chronic hepatitis B, which can progress to liver cirrhosis and hepatocellular carcinoma. HBV has complex interactions with various cell organelles and proteins that ensure effective progeny virus production. We previously reported that a mitochondrial protein, TIMM29, should regulate the HBV life cycle through interactions with the HBV preS1 protein. Here, we established Halo-TIMM29wt-, Halo-TIMM29:∆99–192-, and Halo-TIMM29:92–194-expressing cells using TIMM29-knockout HB611 (TIMM29KO/HB611) cells, a stably HBV-producing cell line based on Huh6 cells. We found that HBV antigen expression and replication were downregulated in cells stably expressing full-length TIMM29, but not in those expressing TIMM29 deletion mutants. On the other hand, in the case of TIMM29-knockout C4 (TIMM29KO/C4), which is a human NTCP-expressing HepG2 cell line that is competent for HBV infection and amplification, these phenomena were not reproduced, except in full-length TIMM29 (Halo-TIMM29wt)-expressing cells. Using gene expression microarrays, we identified downregulation of ARRDC3 and BASP1 in TIMM29KO/HB611 and TIMM29KO/C4. It was suggested that TIMM29 localized at the mitochondrial inner membrane served as a signaling hub, orchestrating the activation of ARRDC3 and BASP1 expression to restrict HBV transcription. The expression of TIMM29 mutants in TIMM29KO/HB611 and TIMM29KO/C4 cells suggested that ARRDC3 was dependent on the HBV preS1-binding region of TIMM29 (amino acids 99–189). In contrast, BASP1 expression varied according to cell type, indicating additional regulatory mechanisms. Thus, this study should significantly advance our understanding of TIMM29-mediated inhibition of HBV amplification and lead to improvements in antiviral strategies and therapeutic interventions against HBV.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 4","pages":"229-246"},"PeriodicalIF":1.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433087","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}
{"title":"Supersulfides: A Promising Therapeutic Approach for Autoinflammatory Diseases","authors":"Tianli Zhang, Touya Toyomoto, Tomohiro Sawa, Takaaki Akaike, Tetsuro Matsunaga","doi":"10.1111/1348-0421.13205","DOIUrl":"10.1111/1348-0421.13205","url":null,"abstract":"<p>Supersulfides are molecular species characterized by catenated sulfur moieties, including low-molecular-weight and protein-bound supersulfides. Emerging evidence suggests that these molecules, abundantly present in diverse organisms, play essential roles far beyond their chemical properties, such as functions in energy metabolism, protein stabilization, and antiviral defense. Recent studies highlight their regulatory effects on pattern-recognition receptors (PRRs) and associated signaling pathways–such as nucleotide oligomerization domain-like receptor signaling, toll-like receptor signaling, and type I interferon receptor signaling–critical for innate immunity and inflammatory responses. Dysregulation of these pathways is implicated in a heterogeneous group of autoinflammatory diseases, including inflammasomopathies, relopathies, and type I interferonopathies, respectively. Notably, both endogenous and synthetic supersulfide donors have recently shown promising inhibitory effects on PRR signaling, offering their potential as targeted therapies for managing autoinflammatory conditions. This review summarizes the fundamental biology of supersulfides and typical autoinflammatory diseases, focusing on their roles in innate immune and inflammatory responses, while exploring their therapeutic potential in these diseases.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 4","pages":"191-202"},"PeriodicalIF":1.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433341","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}
{"title":"Hypoxia-Inducible Factor 1 Alpha Potentiates Lipopolysaccharide-Induced Expression of IL-13 and IL-33 in Mast Cells Under Hypoxia","authors":"Norika Chiba, Tomokazu Ohnishi, Tetsuya Matsuguchi","doi":"10.1111/1348-0421.13202","DOIUrl":"10.1111/1348-0421.13202","url":null,"abstract":"<div>\u0000 \u0000 <p>Lipopolysaccharide (LPS) is an exacerbating factor for allergic airway inflammation at least partly due to the activation of mast cells (MCs). LPS stimulates MCs to express both pro-inflammatory and type 2 cytokines, among which interleukin (IL)-13 is essential for the generation of allergic diseases. LPS also induces the expression of “alarmins” such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) from various cell types including epithelial cells, and increased serum IL-33 levels were reported to correlate with disease severity of asthma. MCs reside in peripheral tissues where the oxygen concentration is significantly lower than that in the air and further decreased by inflammation and bronchoconstriction in asthma. However, the effects of hypoxia on LPS-induced cytokine expression in MCs have not been fully elucidated. Here we show that LPS induces <i>Il4</i>, <i>Il6</i>, <i>Il13</i>, <i>Il33</i>, <i>Tnf</i>, and <i>Tslp</i> mRNAs in MCs. Notably, hypoxia robustly enhanced expressions of <i>Il13</i> and <i>Il33</i>, but not the other cytokines in LPS-stimulated MCs. We also found that this promotive effect is dependent on the presence of hypoxia-inducible factor (HIF) 1α protein. Our study will provide new insight on the role of MCs in the LPS-associated pathogenesis of allergic diseases.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 4","pages":"247-255"},"PeriodicalIF":1.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409118","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":"Serological Evidence of Cetacean Morbillivirus Infection in Common Bottlenose Dolphins in Japan.","authors":"Kaede Tashiro, Takao Segawa, Kiyotaka Konishi, Fumio Seki, Hiroshi Katoh, Toshiaki Ishibashi, Makoto Takeda, Takuya Itou","doi":"10.1111/1348-0421.13207","DOIUrl":"https://doi.org/10.1111/1348-0421.13207","url":null,"abstract":"<p><p>This study revealed that 41.9% of wild-born Japanese captive dolphins (18 out of 43 dolphins) have neutralizing antibodies specific to cetacean morbillivirus (CeMV). This finding indicates a widespread yet undetected CeMV infection among wild dolphins in the waters around Japan, occurring without notable epidemic or mass mortality of dolphins.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414703","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":"A Clinical Isolate of Human Parainfluenza Virus 3 (Fukushima/O695/2019) Contains a Mutation in the Serial Guanosines in the RNA Editing Site of the P Gene and Produces an Atypical Number of Nongenomic Guanosine Insertions During RNA Editing","authors":"Kazuya Shirato, Miyuki Kawase, Reiko Suwa, Masatoshi Kakizaki, Satoko Sugimoto, Yohei Kume, Mina Chishiki, Takashi Ono, Hisao Okabe, Sakurako Norito, Mitsuaki Hosoya, Makoto Ujike, Koichi Hashimoto","doi":"10.1111/1348-0421.13203","DOIUrl":"10.1111/1348-0421.13203","url":null,"abstract":"<div>\u0000 \u0000 <p>Human parainfluenza virus 3 (HPIV3) contains a purine-rich RNA editing site, allowing multiple viral proteins to be produced from a single gene by the posttranscriptional addition of G nucleotides. The Fukushima/O695/2019 (O695) HPIV3 clinical isolate has a G-to-A substitution at the last position of five serial G residues in the RNA editing site. This study evaluates the effects of this substitution in the RNA editing site on the biological character of HPIV3. Our results show that O695 has slightly reduced viral replication compared with viruses with an intact RNA editing site. The number of G nucleotides inserted into the RNA editing site in HPIV3 isolates with an intact RNA editing site was 5 or fewer in most cases, giving a total of 10 serial G bases (5 + 5). In contrast, the number of G nucleotides inserted into the RNA editing site in O695 showed an atypical pattern, with six or fewer in most cases. This resulted in a total of 10 (4 + 6), suggesting the additional insertion of one more nongenomic G to the mRNA of the P gene of O695 compared with viruses carrying no mutations in the RNA editing site. Phylogenetic analysis reveals that mutations in the RNA editing site occur sporadically with various mutation patterns, suggesting that these mutations are routinely selected for during the life cycle of HPIV3.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 4","pages":"220-228"},"PeriodicalIF":1.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399202","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":"Neurofilament Light Chain: A Potential Diagnostic Biomarker for Rabies","authors":"Nayana Siddalingaiah, Lonika Lodha, Manoor Ananda Ashwini, Shubhangi Chandel, Sathya Priya Manuel, Parthipulli Vasuki Prathyusha, Tina Damodar, Sarada Subramanian, Reeta S. Mani","doi":"10.1111/1348-0421.13201","DOIUrl":"10.1111/1348-0421.13201","url":null,"abstract":"<div>\u0000 \u0000 <p>Rabies is a fatal, acute progressive encephalomyelitis caused by the rabies virus and other <i>Lyssaviruses</i>. Several other clinical conditions can mimic rabies. Antemortem laboratory diagnosis remains challenging and requires multiple or serial sampling for confirmation. Measurement of host-based biomarkers is an emerging area of research in infectious diseases; however, a reliable biomarker for rabies remains elusive. In this study, neurofilament light chain (NfL), an established marker of neuronal injury, has been investigated as a potential diagnostic marker for rabies. NfL levels were measured using the Simoa NfL v2 kit in serum and cerebrospinal fluid (CSF) samples received for routine diagnostic testing from encephalitis cases (rabies, <i>n</i> = 31; other encephalitides, <i>n</i> = 30) and controls (<i>n</i> = 24). The median serum NfL level in the rabies group was significantly higher than that in the control group (adjusted <i>p</i> < 0.001), as well as the other encephalitides group (adjusted <i>p</i> = 0.024). Furthermore, the median CSF NfL level in the rabies group was significantly higher than that in the other encephalitides group (<i>p</i> < 0.001). There were no significant differences in serum or CSF NfL levels in rabies cases with different clinical presentations, prior vaccination status, or incubation period. These findings demonstrate for the first time that rabies can be differentiated from other causes of encephalitis by extremely high NfL levels.</p></div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 4","pages":"212-219"},"PeriodicalIF":1.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365226","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":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13134","DOIUrl":"https://doi.org/10.1111/1348-0421.13134","url":null,"abstract":"<p><b>Cover photograph</b>: Cover photograph: Radial SUCRA plot of studied adhesion and biofilm-related genes. The size of nodes represents number of isolates used in the network meta-analysis. <i>Microbiol Immunol: 69:104–113</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 2","pages":"i-ii"},"PeriodicalIF":1.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111413","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}