Transkingdom network reveals bacterial players associated with cervical cancer gene expression program

Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause the disease. Chromosomal amplifications have been identified as a source of upregulation for cervical cancer driver genes but cannot fully explain increased expression of immune genes in invasive carcinoma. Insight into additional factors that may tip the balance from immune tolerance of HPV to the elimination of the virus may lead to better diagnosis markers. We investigated whether microbiota affect molecular pathways in cervical carcinogenesis by performing microbiome analysis via sequencing 16S rRNA in tumor biopsies from 121 patients. While we detected a large number of intra-tumor taxa (289 operational taxonomic units (OTUs)), we focused on the 38 most abundantly represented microbes. To search for microbes and host genes potentially involved in the interaction, we reconstructed a transkingdom network by integrating a previously discovered cervical cancer gene expression network with our bacterial co-abundance network and employed bipartite betweenness centrality. The top ranked microbes were represented by the families Bacillaceae, Halobacteriaceae, and Prevotellaceae. While we could not define the first two families to the species level, Prevotellaceae was assigned to Prevotella bivia. By co-culturing a cervical cancer cell line with P. bivia, we confirmed that three out of the ten top predicted genes in the transkingdom network (lysosomal associated membrane protein 3 (LAMP3), STAT1, TAP1), all regulators of immunological pathways, were upregulated by this microorganism. Therefore, we propose that intra-tumor microbiota may contribute to cervical carcinogenesis through the induction of immune response drivers, including the well-known cancer gene LAMP3

Transkingdom network reveals bacterial players associated with cervical cancer gene expression program

Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause the disease. Chromosomal amplifications have been identified as a source of upregulation for cervical cancer driver genes but cannot fully explain increased expression of immune genes in invasive carcinoma. Insight into additional factors that may tip the balance from immune tolerance of HPV to the elimination of the virus may lead to better diagnosis markers. We investigated whether microbiota affect molecular pathways in cervical carcinogenesis by performing microbiome analysis via sequencing 16S rRNA in tumor biopsies from 121 patients. While we detected a large number of intra-tumor taxa (289 operational taxonomic units (OTUs)), we focused on the 38 most abundantly represented microbes. To search for microbes and host genes potentially involved in the interaction, we reconstructed a transkingdom network by integrating a previously discovered cervical cancer gene expression network with our bacterial co-abundance network and employed bipartite betweenness centrality. The top ranked microbes were represented by the families Bacillaceae, Halobacteriaceae, and Prevotellaceae. While we could not define the first two families to the species level, Prevotellaceae was assigned to Prevotella bivia. By co-culturing a cervical cancer cell line with P. bivia, we confirmed that three out of the ten top predicted genes in the transkingdom network (lysosomal associated membrane protein 3 (LAMP3), STAT1, TAP1), all regulators of immunological pathways, were upregulated by this microorganism. Therefore, we propose that intra-tumor microbiota may contribute to cervical carcinogenesis through the induction of immune response drivers, including the well-known cancer gene LAMP3

Akkermansia muciniphila mediates negative effects of IFN gamma on glucose metabolism.

Submitted by Nuzia Santos ([email protected]) on 2017-04-10T19:08:27Z No. of bitstreams: 1 ve_Greer_Renee_Akkermansia_CPqRR_2016.pdf: 8643774 bytes, checksum: 8c546cd3b0da66b7b71d02a3bdd08763 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-04-10T19:29:03Z (GMT) No. of bitstreams: 1 ve_Greer_Renee_Akkermansia_CPqRR_2016.pdf: 8643774 bytes, checksum: 8c546cd3b0da66b7b71d02a3bdd08763 (MD5)Made available in DSpace on 2017-04-10T19:29:03Z (GMT). No. of bitstreams: 1 ve_Greer_Renee_Akkermansia_CPqRR_2016.pdf: 8643774 bytes, checksum: 8c546cd3b0da66b7b71d02a3bdd08763 (MD5) Previous issue date: 2016Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USAOregon State University. College of Veterinary Medicine. Corvallis, Oregon, USAUniversidade de São Paulo. Escola de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, BrazilOswaldo Cruz Foundation. René Rachou Research Center. Belo Horizonte, MG, BrasilOregon State University. college of Pharmacy. Corvallis, Oregon, USAOregon State University. College of Veterinary Medicine. Corvallis, Oregon, USAUniversity of North Carolina at Chapel Hill. Division of Pediatric Gastroenterology. Chapel Hill, North Carolina, USAUniversity of São Paulo Medical School. Laboratory of Genetics and Molecular Cardiology. Heart Institute. São Paulo, SP, BrazilUniversity of São Paulo Medical School. Laboratory of Genetics and Molecular Cardiology. Heart Institute. São Paulo, SP, BrazilUniversidade de São Paulo. Escola de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, BrazilNational Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USANational Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USANational Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USAOregon State University. College of Pharmacy. Corvallis, Oregon, USADuke University Medical Center. Division of Geriatrics and Center for the Study of Aging and Human Development. Departments of Medicine, Molecular Genetics and Microbiology and Immunology. VA Medical Center. Education and Clinical Center. Geriatric Research. Durham, North Carolina, USAUniversity of North Carolina at Chapel Hill. Division of Pediatric Gastroenterology. Chapel Hill, North Carolina, USAOregon State University. College of Pharmacy. Corvallis, Oregon, USAOregon State University. College of Veterinary Medicine. Corvallis, Oregon, USACross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFN gamma on glucose tolerance. In IFN gamma-deficient mice, A. muciniphila is significantly increased and restoration of IFN gamma levels reduces A. muciniphila abundance. We further show that IFN gamma-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFN gamma-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFN gamma-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFN gamma, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and human

Reduced Degranulation of NK Cells in Patients with Frequently Recurring Herpes ▿

NK cells lyse virus-infected cells by degranulation; however, alterations in NK cell degranulation in persistent viral infections have not been directly studied. Earlier reports have documented a decrease in NK activity in patients with frequently recurring herpes (FRH). We corroborate these findings by showing that the degranulation responses of blood NK cells from patients with FRH, both during relapse and during remission, are significantly lower than those in healthy donors. The impaired degranulation was probably not caused by defective target cell recognition, since it was observed upon stimulation both with K562 cells and with a receptor-independent stimulus (phorbol 12-myristate 13-acetate plus ionomycin). We also show that the intracellular expression of perforin and CD107a by NK cells from patients with FRH is not different from that in healthy donors, thus excluding that the low NK cell degranulation in FRH is caused by a smaller size of the lytic granule compartment. We confirm previous reports on lowered NK activity in FRH patients and show that NK activity is significantly impaired only during remission, but not relapse; the causes for the discrepancy between the low degranulation and “normal” NK cell activity during relapse are discussed. In all, these data point at the deficit of NK cell degranulation in FRH. Whether this is a predisposing factor or a consequence of herpes simplex virus infection requires further investigation

Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell-deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans

Современные подходы к ведению пациентов с крапивницей

The Union of Pediatricians of Russia together with the Russian Association of Allergologists and Clinical Immunologists and the Russian Society of Dermatovenerologists and Cosmetologists have developed new clinical guidelines for the urticaria in adults and children. Urticaria is a common disease; its various clinical variants are diagnosed in 15–25% of people in the global population, and a quarter of all cases belongs to chronic urticaria. The prevalence of acute urticaria is 20%, and 2.1–6.7% in child population, whereas acute urticaria is more common in children than in adults. The prevalence of chronic urticaria in adults in the general population is 0.7 and 1.4%, and 1.1% in children under 15 years of age, according to the systematic review and meta-analysis, respectively. This article covers features of epidemiology, etiology, and pathogenesis of the disease with particular focus on differential diagnostic search. Guidelines on treatment and step-by-step therapy scheme (both based on principles of evidencebased medicine) for pediatric patients were presented. Clarification on the analysis of the therapy efficacy and the degree of disease activity was given.Союзом педиатров России совместно с Российской ассоциацией аллергологов и иммунологов и Российским обществом дерматовенерологов и косметологов (РОДВК) разработаны новые клинические рекомендации для диагноза «крапивница» для взрослых и детей. Крапивница является распространенным заболеванием: различные ее клинические варианты диагностируются у 15–25% людей в популяции, при этом четверть случаев приходится на хроническую крапивницу. Распространенность острой крапивницы составляет 20%, среди детского населения — 2,1–6,7%, при этом острая крапивница у детей встречается чаще, чем у взрослых. По данным систематического обзора и мета-анализа, хроническая крапивница у взрослых в общей популяции составляет 0,7 и 1,4% соответственно, у детей до 15 лет — до 1,1%. В статье рассматриваются особенности эпидемиологии, этиологии и патогенеза заболевания, особое внимание уделено вопросам дифференциально-диагностического поиска. Для пациентов детского возраста приведены рекомендации по лечению согласно принципам доказательной медицины и предложена ступенчатая схема терапии. Дано четкое разъяснение к проведению анализа эффективности терапии и оценки степени активности заболевания