Current topics in microbiology and immunology最新文献

{"title":"Helicobacter pylori-Induced Host Cell DNA Damage and Genetics of Gastric Cancer Development.","authors":"Steffen Backert, Bodo Linz, Nicole Tegtmeyer","doi":"10.1007/978-3-031-47331-9_7","DOIUrl":"10.1007/978-3-031-47331-9_7","url":null,"abstract":"<p><p>Gastric cancer is a very serious and deadly disease worldwide with about one million new cases every year. Most gastric cancer subtypes are associated with genetic and epigenetic aberrations caused by chromosome instability, microsatellite instability or Epstein-Barr virus infection. Another risk factor is an infection with Helicobacter pylori, which also triggers severe alterations in the host genome. This pathogen expresses an extraordinary repertoire of virulence determinants that take over control of important host cell signaling functions. In fact, H. pylori is a paradigm of persistent infection, chronic inflammation and cellular destruction. In particular, H. pylori profoundly induces chromosomal DNA damage by introducing double-strand breaks (DSBs) followed by genomic instability. DSBs appear in response to oxidative stress and pro-inflammatory transcription during the S-phase of the epithelial cell cycle, which mainly depends on the presence of the bacterial cag pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). This scenario is closely connected with the T4SS-mediated injection of ADP-glycero-β-D-manno-heptose (ADP-heptose) and oncoprotein CagA. While ADP-heptose links transcription factor NF-κB-induced innate immune signaling with RNA-loop-mediated DNA replication stress and introduction of DSBs, intracellular CagA targets the tumor suppressor BRCA1. The latter scenario promotes BRCAness, a disease characterized by the deficiency of effective DSB repair. In addition, genetic studies of patients demonstrated the presence of gastric cancer-associated single nucleotide polymorphisms (SNPs) in immune-regulatory and other genes as well as specific pathogenic germline variants in several crucial genes involved in homologous recombination and DNA repair, all of which are connected to H. pylori infection. Here we review the molecular mechanisms leading to chromosomal DNA damage and specific genetic aberrations in the presence or absence of H. pylori infection, and discuss their importance in gastric carcinogenesis.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development.","authors":"Lydia E Wroblewski, Richard M Peek","doi":"10.1007/978-3-031-47331-9_2","DOIUrl":"10.1007/978-3-031-47331-9_2","url":null,"abstract":"<p><p>The human pathogen Helicobacter pylori is the strongest known risk factor for gastric disease and cancer, and gastric cancer remains a leading cause of cancer-related death across the globe. Carcinogenic mechanisms associated with H. pylori are multifactorial and are driven by bacterial virulence constituents, host immune responses, environmental factors such as iron and salt, and the microbiota. Infection with strains that harbor the cytotoxin-associated genes (cag) pathogenicity island, which encodes a type IV secretion system (T4SS) confer increased risk for developing more severe gastric diseases. Other important H. pylori virulence factors that augment disease progression include vacuolating cytotoxin A (VacA), specifically type s1m1 vacA alleles, serine protease HtrA, and the outer-membrane adhesins HopQ, BabA, SabA and OipA. Additional risk factors for gastric cancer include dietary factors such as diets that are high in salt or low in iron, H. pylori-induced perturbations of the gastric microbiome, host genetic polymorphisms, and infection with Epstein-Barr virus. This chapter discusses in detail host factors and how H. pylori virulence factors augment the risk of developing gastric cancer in human patients as well as how the Mongolian gerbil model has been used to define mechanisms of H. pylori-induced inflammation and cancer.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in HIV Infection.","authors":"Marcus Altfeld,&nbsp;Eileen P Scully","doi":"10.1007/978-3-031-35139-6_3","DOIUrl":"10.1007/978-3-031-35139-6_3","url":null,"abstract":"<p><p>Biological sex has wide-ranging impacts on HIV infection spanning differences in acquisition risk, the pathogenesis of untreated infection, impact of chronic treated disease and prospects for HIV eradication or functional cure. This chapter summarizes the scope of these differences and discusses several features of the immune response thought to contribute to the clinical outcomes.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of Sex Differences in Immunity.","authors":"Shani T Gal-Oz,&nbsp;Tal Shay","doi":"10.1007/978-3-031-35139-6_1","DOIUrl":"10.1007/978-3-031-35139-6_1","url":null,"abstract":"<p><p>Women have a stronger immune response and a higher frequency of most autoimmune diseases than men. While much of the difference between men and women is due to the effect of gonadal hormones, genetic differences play a major role in the difference between the immune response and disease frequencies in women and men. Here, we focus on the immune differences between the sexes that are not downstream of the gonadal hormones. These differences include the gene content of the sex chromosomes, the inactivation of chromosome X in women, the consequences of non-random X inactivation and escape from inactivation, and the states that are uniquely met by the immune system of women-pregnancy, birth, and breast feeding. While these female-specific states are temporary and involve gonadal hormonal changes, they may leave a long-lasting footprint on the health of women, for example, by fetal cells that remain in the mother's body for decades. We also briefly discuss the immune phenotype of congenital sex chromosomal aberrations and experimental models that enable hormonal and the non-hormonal effects of the sex chromosomes to be disentangled. The increasing human life expectancy lengthens the period during which gonadal hormones levels are reduced in both sexes. A better understanding of the non-hormonal effects of sex chromosomes thus becomes more important for improving the life quality during that period.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of MHC and MHC-Like Molecules by Varicella Zoster Virus.","authors":"Allison Abendroth,&nbsp;Barry Slobedman","doi":"10.1007/82_2022_254","DOIUrl":"https://doi.org/10.1007/82_2022_254","url":null,"abstract":"<p><p>Varicella zoster virus (VZV) is a medically important human herpesvirus that has co-evolved with the human host to become a highly successful and ubiquitous pathogen. Whilst it is clear the innate and adaptive arms of the immune response play key roles in controlling this virus during both primary and reactivated infections, it is also apparent that VZV \"fights back\" by encoding multiple functions that impair a wide range of immune molecules. This capacity to manipulate the immune response is likely to be important in underpinning the success of VZV as a human pathogen. In this review, we will focus on the plethora of mechanisms that VZV has evolved to prevent and/or delay immune functions via regulating the expression of major histocompatibility complex (MHC) class I and MHC class II molecules, as well as several MHC-like molecules. In doing so, we will highlight both established and newly emerged VZV-encoded immunomodulatory capabilities and provide context to new avenues of research that seek to build the most comprehensive understanding of how this virus interfaces with these aspects of host immunity.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40327263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Management of Gastric Cancer Treatment Regimens.","authors":"Juliette Boilève, Yann Touchefeu, Tamara Matysiak-Budnik","doi":"10.1007/978-3-031-47331-9_11","DOIUrl":"10.1007/978-3-031-47331-9_11","url":null,"abstract":"<p><p>Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer-associated death in the world. Endoscopic resection can be the treatment in selected cases of very early gastric cancer. Surgery is recommended for tumors that do not meet the criteria for endoscopic resection or for tumors with lymph node invasion but without distant metastases. Gastrectomy should include D2 lymphadenectomy without splenectomy. Perioperative or adjuvant chemotherapy improves survival and is recommended in locally advanced gastric cancer (>T1 and/or with lymph nodes positive). In locally advanced cancer with microsatellite instability (MSI), immunotherapy should be considered. Advanced unresectable or metastatic gastric cancer has a poor prognosis. The basis of the treatment is cytotoxic chemotherapy, with platinum and fluoropyrimidine doublet in the first line. Targeted therapies can be combined with chemotherapy. Trastuzumab (anti-HER2) is recommended in the first line in HER2-positive cancer. Ramucirumab (anti-VEGFR2) is recommended in the second line, in addition to paclitaxel chemotherapy. Zolbetuximab (anti-Claudine 18.2) should also be considered in the first line in Claudine 18.2-positive cancer. Immunotherapy can also be associated with chemotherapy in the first line of PD-L1-positive cancer. In HER2-positive and PD-L1-positive cancer, adjunction of trastuzumab and immunotherapy should be considered. In advanced and metastatic cancer with microsatellite instability (MSI), immunotherapy should be the first choice depending on its availability. Important progress has been made in recent years in the treatment of gastric cancer, especially due to a better understanding of molecular characteristics and heterogeneity of this disease. New targets and therapeutic approaches are being developed, which will very likely lead to changes in the management of gastric cancer.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric Stem Cell Biology and Helicobacter pylori Infection.","authors":"Jonas Wizenty, Michael Sigal","doi":"10.1007/978-3-031-47331-9_1","DOIUrl":"10.1007/978-3-031-47331-9_1","url":null,"abstract":"<p><p>Helicobacter pylori colonizes the human gastric mucosa and persists lifelong. An interactive network between the bacteria and host cells shapes a unique microbial niche within gastric glands that alters epithelial behavior, leading to pathologies such as chronic gastritis and eventually gastric cancer. Gland colonization by the bacterium initiates aberrant trajectories by inducing long-term inflammatory and regenerative gland responses, which involve various specialized epithelial and stromal cells. Recent studies using cell lineage tracing, organoids and scRNA-seq techniques have significantly advanced our knowledge of the molecular \"identity\" of epithelial and stromal cell subtypes during normal homeostasis and upon infection, and revealed the principles that underly stem cell (niche) behavior under homeostatic conditions as well as upon H. pylori infection. The activation of long-lived stem cells deep in the gastric glands has emerged as a key prerequisite of H. pylori-associated gastric site-specific pathologies such as hyperplasia in the antrum, and atrophy or metaplasia in the corpus, that are considered premalignant lesions. In addition to altering the behaviour of bona fide stem cells, injury-driven de-differentiation and trans-differentation programs, such as \"paligenosis\", subsequently allow highly specialized secretory cells to re-acquire stem cell functions, driving gland regeneration. This plastic regenerative capacity of gastric glands is required to maintain homeostasis and repair mucosal injuries. However, these processes are co-opted in the context of stepwise malignant transformation in chronic H. pylori infection, causing the emergence, selection and expansion of cancer-promoting stem cells.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunology of Pregnancy and Systemic Consequences.","authors":"Fiona M Menzies","doi":"10.1007/978-3-031-35139-6_10","DOIUrl":"10.1007/978-3-031-35139-6_10","url":null,"abstract":"<p><p>Pregnancy is an immunological paradox, with renowned Nobel Prize winning transplantation biologist Sir Peter Brian Medawar being the first to introduce this concept back in 1953. This concept considers how the maternal immune system can tolerate the developing fetus, which is 50% antigenically foreign to the uterus. There have been significant advances in our understanding of the immune system in regulating fertility, pregnancy and in complications of these, and what was once considered a paradox can be seen as a highly evolved system. Indeed, the complexity of the maternal-fetal interface along with our ever-advancing knowledge of immune cells and mediators means that we have a better understanding of these interactions, with gaps still present.  This chapter will summarise the key aspects of the role of the immune system at each stage of pregnancy and highlight the recent advances in our knowledge.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10221031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome Structure, Life Cycle, and Taxonomy of Coronaviruses and the Evolution of SARS-CoV-2.","authors":"Kevin Lamkiewicz,&nbsp;Luis Roger Esquivel Gomez,&nbsp;Denise Kühnert,&nbsp;Manja Marz","doi":"10.1007/978-3-031-15640-3_9","DOIUrl":"https://doi.org/10.1007/978-3-031-15640-3_9","url":null,"abstract":"<p><p>Coronaviruses have a broad host range and exhibit high zoonotic potential. In this chapter, we describe their genomic organization in terms of encoded proteins and provide an introduction to the peculiar discontinuous transcription mechanism. Further, we present evolutionary conserved genomic RNA secondary structure features, which are involved in the complex replication mechanism. With a focus on computational methods, we review the emergence of SARS-CoV-2 starting with the 2019 strains. In that context, we also discuss the debated hypothesis of whether SARS-CoV-2 was created in a laboratory. We focus on the molecular evolution and the epidemiological dynamics of this recently emerged pathogen and we explain how variants of concern are detected and characterised. COVID-19, the disease caused by SARS-CoV-2, can spread through different transmission routes and also depends on a number of risk factors. We describe how current computational models of viral epidemiology, or more specifically, phylodynamics, have facilitated and will continue to enable a better understanding of the epidemic dynamics of SARS-CoV-2.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10474584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZBP1/DAI-Dependent Cell Death Pathways in Influenza A Virus Immunity and Pathogenesis.","authors":"Paul G Thomas, Maria Shubina, Siddharth Balachandran","doi":"10.1007/82_2019_190","DOIUrl":"10.1007/82_2019_190","url":null,"abstract":"<p><p>Influenza A viruses (IAV) are members of the Orthomyxoviridae family of negative-sense RNA viruses. The greatest diversity of IAV strains is found in aquatic birds, but a subset of strains infects other avian as well as mammalian species, including humans. In aquatic birds, infection is largely restricted to the gastrointestinal tract and spread is through feces, while in humans and other mammals, respiratory epithelial cells are the primary sites supporting productive replication and transmission. IAV triggers the death of most cell types in which it replicates, both in culture and in vivo. When well controlled, such cell death is considered an effective host defense mechanism that eliminates infected cells and limits virus spread. Unchecked or inopportune cell death also results in immunopathology. In this chapter, we discuss the impact of cell death in restricting virus spread, supporting the adaptive immune response and driving pathogenesis in the mammalian respiratory tract. Recent studies have begun to shed light on the signaling pathways underlying IAV-activated cell death. These pathways, initiated by the pathogen sensor protein ZBP1 (also called DAI and DLM1), cause infected cells to undergo apoptosis, necroptosis, and pyroptosis. We outline mechanisms of ZBP1-mediated cell death signaling following IAV infection.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/82_2019_190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37569772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}