{"title":"Predictive value of CXCL10 for the occurrence of immune-related adverse events in patient with renal cell carcinoma","authors":"Yuji Miura, Takanobu Motoshima, Toshiki Anami, Hiromu Yano, Remi Mito, Cheng Pan, Shinji Urakami, Keiichi Kinowaki, Hirotake Tsukamoto, Ryoma Kurahashi, Yoji Murakami, Junji Yatsuda, Yukio Fujiwara, Tomomi Kamba, Yoshihiro Komohara","doi":"10.1111/1348-0421.13067","DOIUrl":"10.1111/1348-0421.13067","url":null,"abstract":"<p>Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti-CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C–X–C motif) ligand (CXCL) 1, IL-17A, IL-1β, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post–dose 1. Only CXCL10, at post–dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (<i>P</i> = 0.0413). Plasma CXCL10 levels were then measured at baseline and post–dose 1 in an extended cohort of 43 patients with RCC who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post–dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (<i>P</i> = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post–dose 1 (<i>P</i> = 0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 7","pages":"345-354"},"PeriodicalIF":2.6,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101576","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":"Immunization with autotransporter Vag8 prevents coughing induced by Bordetella pertussis infection in mice","authors":"Koichiro Suzuki, Yukihiro Hiramatsu, Takashi Nishida, Yasuhiko Horiguchi","doi":"10.1111/1348-0421.13066","DOIUrl":"10.1111/1348-0421.13066","url":null,"abstract":"<p><i>Bordetella pertussis</i> causes pertussis, which is characterized by paroxysmal coughing. This disease is generally prevented through vaccination; however, the number of pertussis cases is increasing worldwide despite high vaccination coverage. We previously reported that an autotransporter of <i>B. pertussis</i>, virulence-associated gene 8 (Vag8), causes coughing in combination with pertussis toxin and lipooligosaccharide. Here, we show that immunization with Vag8 protected mice from coughing after <i>B. pertussis</i> infection and enhanced the efficacy of a current pertussis vaccine containing pertussis toxoid against the cough. Our findings indicate that Vag8 could be a vaccine antigen to prevent pertussis cough.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 6","pages":"314-317"},"PeriodicalIF":2.6,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580086","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":"Human cytomegalovirus infection activates NLRP3 inflammasome by releasing mtDNA into the cytosol in human THP-1 cells","authors":"Xi Xu, Junwen Cai, Xiaoming Wang, Yutian Lu, Binhan Guo, Meimei Lai, Linhua Lan, Ying Peng, Xiaoqun Zheng","doi":"10.1111/1348-0421.13063","DOIUrl":"10.1111/1348-0421.13063","url":null,"abstract":"<p>Human cytomegalovirus (HCMV) infection of monocytes results in the production of inflammatory cytokine through inflammasome. However, the mechanism of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in HCMV infection remains unclear. In this study, HCMV infection promoted the increase of mitochondrial fusion and caused mitochondrial dysfunction in THP-1 cells, including excessive reactive oxygen species production and decreased mitochondrial membrane potential (Δψm). Meanwhile, the expression of mitochondrial DNA (mtDNA)-binding protein TFAM (transcription factor A, mitochondrial) was decreased and mtDNA content in the cytoplasm was increased. Knockdown of TFAM caused an increase in mtDNA copy number in the cytoplasm and resulted in elevated NLRP3 expression, active caspase-1, and mature IL-1β. After a 3 h treatment with MCC950, an NLRP3 inhibitor, the increase of cleaved caspase-1 and mature IL-1β were suppressed. Besides, overexpression of TFAM inhibited the expression of NLRP3, cleaved caspase-1, and mature IL-1β. In addition, knockdown of NLRP3 inhibited the IL-1β process after HCMV infection. mtDNA-deficient cells showed a limited ability to produce NLRP3 and process IL-1β after HCMV infection. In conclusion, HCMV infection of THP-1 cells resulted in decreased mitochondrial TFAM protein expression and increased mtDNA release into the cytoplasm, which eventually led to the activation of NLRP3 inflammasome.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 6","pages":"303-313"},"PeriodicalIF":2.6,"publicationDate":"2023-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696027","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}
Chie Aoki-Utsubo, Puguh Indrasetiawan, Kento Fukano, Masamichi Muramatsu, Nina Artanti, Muhammad Hanafi, Hak Hotta, Masanori Kameoka
{"title":"Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells","authors":"Chie Aoki-Utsubo, Puguh Indrasetiawan, Kento Fukano, Masamichi Muramatsu, Nina Artanti, Muhammad Hanafi, Hak Hotta, Masanori Kameoka","doi":"10.1111/1348-0421.13064","DOIUrl":"10.1111/1348-0421.13064","url":null,"abstract":"<p>Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)–mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 6","pages":"281-292"},"PeriodicalIF":2.6,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953549","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":"Nicotine- and tar-removed cigarette smoke extract modulates the antigen presentation function of mouse bone marrow-derived dendritic cells","authors":"Kazuyuki Furuta, Takehiro Yoshioka, Kana Nishikaze, Noriko Yoshikawa, Kazuki Nakamura, Chikara Kaito","doi":"10.1111/1348-0421.13061","DOIUrl":"10.1111/1348-0421.13061","url":null,"abstract":"<p>Dendritic cells (DCs) take up antigens derived from pathogens such as bacteria and viruses, and from tumor cells and induce the activation of antigen-specific T cells through major histocompatibility complex (MHC)-mediated antigen presentation. Mainstream cigarette smoke extract (CSE) has various effects, and the effects of its major components, nicotine and tar, have been analyzed extensively. Recently, the physiological effects of nicotine- and tar-removed CSE (cCSE) have also been reported. However, the effects of cCSE on DC-mediated immune responses remain unknown. In this study, we found that cCSE enhanced lipopolysaccharide (LPS)-stimulated induction of the expression of MHC-I and MHC-II on the cell surface of mouse bone marrow-derived DCs (BMDCs). In contrast, cCSE suppressed the induction of CD86 induced by stimulation with curdlan and interferon-γ (IFN-γ). In addition, cCSE suppressed the production of IL-12, IL-23, and IL-10 by LPS and curdlan stimulation. In the presence of cCSE, LPS-stimulated BMDCs showed enhanced activation of CD4 and CD8 T cells and increased IL-2 production from T cells by antigen presentation in a mixed-leukocyte reaction assay. In contrast, cCSE did not affect the activation of T cells by curdlan- or IFN-γ-stimulated BMDCs, and curdlan-stimulated BMDCs suppressed IL-17 production from T cells and enhanced IFN-γ production. These results suggest that cCSE has different effects on the activation signals induced by LPS, curdlan, and IFN-γ in BMDCs and modulates the antigen presentation function of BMDCs.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 5","pages":"264-273"},"PeriodicalIF":2.6,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755557","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":"Recent advances in studies on magnetosome-associated proteins composing the bacterial geomagnetic sensor organelle","authors":"Azuma Taoka, Yukako Eguchi, Rino Shimoshige, Yoshihiro Fukumori","doi":"10.1111/1348-0421.13062","DOIUrl":"10.1111/1348-0421.13062","url":null,"abstract":"<p>Magnetotactic bacteria (MTB) generate a membrane-enclosed subcellular compartment called magnetosome, which contains a biomineralized magnetite or greigite crystal, an inner membrane–derived lipid bilayer membrane, and a set of specifically targeted associated proteins. Magnetosomes are formed by a group of magnetosome-associated proteins encoded in a genomic region called magnetosome island. Magnetosomes are then arranged in a linear chain–like positioning, and the resulting magnetic dipole of the chain functions as a geomagnetic sensor for magneto-aerotaxis motility. Recent metagenomic analyses of environmental specimens shed light on the sizable phylogenetical diversity of uncultured MTB at the phylum level. These findings have led to a better understanding of the diversity and conservation of magnetosome-associated proteins. This review provides an overview of magnetosomes and magnetosome-associated proteins and introduces recent topics about this fascinating magnetic bacterial organelle.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 5","pages":"228-238"},"PeriodicalIF":2.6,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755556","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":"Molecular mechanism of Streptococcus pneumoniae–targeting xenophagy recognition and evasion: Reinterpretation of pneumococci as intracellular bacteria","authors":"Michinaga Ogawa, Sayaka Shizukuishi, Yukihiro Akeda, Makoto Ohnishi","doi":"10.1111/1348-0421.13060","DOIUrl":"10.1111/1348-0421.13060","url":null,"abstract":"<p><i>Streptococcus pneumoniae</i> is a major, encapsulated Gram-positive pathogen that causes diseases including community-acquired pneumonia, meningitis, and sepsis. This pathogen colonizes the nasopharyngeal epithelia asymptomatically but can often migrate to sterile tissues and cause life-threatening invasive infections (invasive pneumococcal disease). Although multivalent pneumococcal polysaccharides and conjugate vaccines are available and effective, they also have major shortcomings with respect to the emergence of vaccine-resistant serotypes. Therefore, alternative therapeutic approaches are needed, and the molecular analysis of host–pathogen interactions and their applications to pharmaceutical development and clinical practice has recently received increased attention. In this review, we introduce pneumococcal surface virulence factors involved in pathogenicity and highlight recent advances in our understanding of host autophagy recognition mechanisms against intracellular <i>S. pneumoniae</i> and pneumococcal evasion from autophagy.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 5","pages":"224-227"},"PeriodicalIF":2.6,"publicationDate":"2023-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9459248","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":"γδ T-cell–mediated immune responses to malaria","authors":"Ganchimeg Bayarsaikhan, Yarob Ibraheem, Shin-Ichi Inoue","doi":"10.1111/1348-0421.13059","DOIUrl":"10.1111/1348-0421.13059","url":null,"abstract":"<p>Malaria is one of the deadliest infectious diseases. Licensed vaccine have demonstrated just over 30% efficacy, and therefore, developing new vaccine candidates and understanding immune responses to <i>Plasmodium</i> have become necessary. γδ T cells have been suggested to be associated with immune responses to malaria due to the observation of their expansion in patients with malaria and experimental models of malaria. γδ T cells act as both “innate-like” and “adaptive-like” cells during immune response to malaria. Studies have found that γδ T cells can recognize <i>Plasmodium</i> phosphoantigen, present the antigen, and initiate adaptive immune response during blood-stage <i>Plasmodium</i> infection. Recent reports also suggested the phagocytic and cytotoxic potential of γδ T cells. Furthermore, γδ T cells can provide protection upon immunization with whole parasite. In addition, γδ T cells during the liver-stage infection were able to prevent experimental cerebral malaria. Despite these new findings, questions related to γδ T-cell response during <i>Plasmodium</i> infection remain to be answered. However, investigating these cells in humans remains difficult in many ways; in this regard, rodent models of malarial infection enable us to study these cells in more detail. Insights from experimental malaria models give rise to new cues for development of malarial vaccine and adjunctive therapy for severe malaria. Here, we review our current knowledge of γδ T-cell immune function in human and experimental mouse malarial infection models; especially, we focus on the mechanisms underlying γδ T cells that are associated with protective immunity during malarial infection.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 5","pages":"239-247"},"PeriodicalIF":2.6,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755541","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}
Abdullah A. K. Alzahrani, Yasser A. Altalhi, Ahmed A. S. Alghamdi, Samah M. Muhandis, Daifallah M. Al Aboud, Gaber M. G. Shehab, Ahmed S. Abdel-Moneim
{"title":"Premarital screening of the viral hepatitis among Saudi nationals","authors":"Abdullah A. K. Alzahrani, Yasser A. Altalhi, Ahmed A. S. Alghamdi, Samah M. Muhandis, Daifallah M. Al Aboud, Gaber M. G. Shehab, Ahmed S. Abdel-Moneim","doi":"10.1111/1348-0421.13058","DOIUrl":"10.1111/1348-0421.13058","url":null,"abstract":"<p>Blood borne sexually transmitted infections are among the most serious health problems worldwide. Many people possessing these infections do not have symptoms and may remain undiagnosed. The current study aimed to screen premaritally the incidence of blood borne viruses among Saudi nationals. A retrospective longitudinal study was conducted, using a total of 91,000 medical records, in the blood bank from a single center in the Western region of Saudi Arabia. All persons who underwent premarital examination during the period 2016–2021 for the presence of hepatitis B and C viruses as a part of the national screening program in Saudi Arabia were included in the study. Serological tests were used to screen the presence of HBc Ab and HBs Ag. Both anti-HCV antibodies and the presence of virus RNA using real-time reverse transcriptase polymerase chain reaction (RT-PCR) were also performed. The study reported the presence of 378/91000 (0.42%) infections with hepatitis B virus (HBV) as indicated by the presence of HBc Ab and HBs Ag. Meanwhile, 208 (0.23%) cases were found to be exposed to HCV including 49/91000 (0.05%) active HCV cases, positive for the HCV RNA, while 159/91000 (0.17%) persons were found to possess positive HCV antibodies in the absence of detectable HCV RNA. It was concluded that there is a low prevalence of HBV and HBV among Saudi citizens who were subjected to premarital screening.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"67 5","pages":"258-263"},"PeriodicalIF":2.6,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9395577","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}