Ilaria Galliano, Cristina Calvi, Marzia Pavan, Anna Pau, Katia Mareschi, Anna Massobrio, Stefano Gambarino, Roberto Albiani, Claudia Linari, Anna Clemente, Paola Montanari, Massimiliano Bergallo
{"title":"Cell-Type-Specific Expression of Human Endogenous Retroviruses and Epigenetic Regulators in Human Peripheral Blood","authors":"Ilaria Galliano, Cristina Calvi, Marzia Pavan, Anna Pau, Katia Mareschi, Anna Massobrio, Stefano Gambarino, Roberto Albiani, Claudia Linari, Anna Clemente, Paola Montanari, Massimiliano Bergallo","doi":"10.1111/apm.70204","DOIUrl":"10.1111/apm.70204","url":null,"abstract":"<div>\u0000 \u0000 <p>Human endogenous retroviruses (HERVs) constitute a substantial fraction of the human genome and are tightly regulated by epigenetic mechanisms. Although HERV transcription has been detected in peripheral blood and shown to vary across immune cell types, including during immune cell differentiation, the contribution of specific circulating blood cell subsets to whole-blood HERV expression remains insufficiently defined. In this study, we quantified the transcriptional levels of HERV-H, HERV-K, and HERV-W pol genes, together with the epigenetic regulators SETDB1 and TRIM28, in purified peripheral blood mononuclear cells (PBMCs), granulocytes, reticulocytes, and platelets from healthy donors using quantitative real-time PCR. Gene expression was normalized per 1 × 10<sup>6</sup> cells to allow direct comparison across cell types. HERV transcripts were predominantly detected in leukocytes, whereas reticulocytes and platelets exhibited minimal expression. Within leukocytes, granulocytes displayed significantly higher HERV expression than PBMCs, despite comparable levels of SETDB1 and TRIM28. These findings demonstrate that HERV transcription in peripheral blood is highly cell-type-specific and largely attributable to granulocytes, providing a framework for interpreting whole-blood HERV measurements and highlighting the importance of accounting for blood cell composition in translational studies.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653445","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}
Gitte A. Pedersen, Benjamin B. Green, Camilla Merrild, Søren H. Elsborg, Mia G. Madsen, Anna K. Keller, Henricus A. M. Mutsaers, Rikke Nørregaard, Lene N. Nejsum
{"title":"Evaluation of Epithelial Integrity in Human Precision-Cut Kidney Slices","authors":"Gitte A. Pedersen, Benjamin B. Green, Camilla Merrild, Søren H. Elsborg, Mia G. Madsen, Anna K. Keller, Henricus A. M. Mutsaers, Rikke Nørregaard, Lene N. Nejsum","doi":"10.1111/apm.70205","DOIUrl":"10.1111/apm.70205","url":null,"abstract":"<p>Renal epithelial cells are pivotal in renal regulation of body fluid and electrolyte balance. While rodent models are commonly used to study renal physiology, species-specific differences limit their translational relevance. To bridge this gap, we used human precision-cut kidney slices (PCKS), an ex vivo tissue-based model that maintains native tissue architecture and cellular diversity. This study had two aims: (1) to determine whether PCKS preserve short-term aquaporin-2 (AQP2) trafficking in response to desmopressin (dDAVP), and (2) to assess whether cortical PCKS maintain epithelial integrity during 24–48 h incubation. In medullary PCKS, 30 min dDAVP stimulation resulted in accumulation of AQP2 at the apical membrane, indicating preserved signaling. In cortical PCKS, AQP2 already showed substantial apical localization under baseline conditions, and no additional redistribution was detected after dDAVP stimulation. In cortical PCKS, incubation for 24 h and 48 h led to mislocalization of AQP2, the Na/K-ATPase and uromodulin, and to altered localization of the adhesion proteins E-cadherin and N-cadherin and the tight junction protein ZO-1 with a shift towards apical localization, indicating loss of epithelial integrity. Thus, short-term signaling was preserved at 30 min, whereas epithelial transport and adhesion proteins became mislocalized after 24–48 h in human PCKS.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653422","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":"Incidence of Cefotaxime-Resistant Haemophilus influenzae Is Linked to Regional Consumption of Oral Aminopenicillins and Parenteral Third-Generation Cephalosporins in Norway","authors":"Dagfinn Skaare, Gunnar Skov Simonsen","doi":"10.1111/apm.70201","DOIUrl":"10.1111/apm.70201","url":null,"abstract":"<p>The emergence of cefotaxime-resistant <i>Haemophilus influenzae</i> (CRHI) in Norway during the 2000s coincided with increased use of oral aminopenicillins and parenteral third-generation cephalosporins. This study examined associations between beta-lactam consumption and CRHI incidence. Surveillance data on antibiotic usage across Norwegian regions (2013–2017) and CRHI incidence in hospitalised patients (January 2013–March 2018) from a previous study were analysed. Correlations were calculated between average consumption rates for aminopenicillins and third-generation cephalosporins, and average CRHI incidence rates. Regional aminopenicillin prescription and hospital sales of third-generation cephalosporins varied substantially. CRHI incidence ranged from 0.8 to 3.2 cases per million inhabitants per year and was significantly associated with use of oral aminopenicillins in primary care (<i>r</i> = 0.88, <i>p</i> = 0.022), hospital use of third-generation cephalosporins (<i>r</i> = 0.88, <i>p</i> = 0.019), and both variables combined (<i>r</i> = 0.89, <i>p</i> = 0.007). The consumption variables also showed significant covariation (<i>r</i> = 0.88, <i>p</i> = 0.020). Regional variation in consumption of oral aminopenicillins and parenteral third-generation cephalosporins is linked to CRHI incidence in Norway. These findings strengthen the evidence base for avoiding unnecessary use of these agents and underscore the need for coordinated antibiotic stewardship across healthcare sectors to limit resistance development.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621700","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}
Peter Østrup Jensen, Mads Lichtenberg, Regitze Lund Nielsen, Blaine Gabriel Fritz, Thomas Bjarnsholt, Tim Holm Jakobsen
{"title":"Density-Dependent Modulation of the Oxidative Burst by Neutrophils in Response to Planktonic and Biofilm Growing Pseudomonas aeruginosa: When Less Is More.","authors":"Peter Østrup Jensen, Mads Lichtenberg, Regitze Lund Nielsen, Blaine Gabriel Fritz, Thomas Bjarnsholt, Tim Holm Jakobsen","doi":"10.1111/apm.70210","DOIUrl":"10.1111/apm.70210","url":null,"abstract":"<p><p>The neutrophilic response to chronic Pseudomonas aeruginosa lung infection is strongly associated with collateral tissue damage impairing lung function in people with cystic fibrosis (pwCF). We recently demonstrated the concurrent presence of both biofilm bacteria and planktonic bacteria in chronically infected lungs in pwCF. However, the neutrophilic response to these distinct bacterial forms remains insufficiently characterized. To investigate this, we fractionated P. aeruginosa batch-cultures to enrich for biofilm or planktonic cells. Confocal microscopy showed that aggregates > 30 μm made up > 92.5% of biofilm biomass, while aggregates < 10 μm comprised > 95% of planktonic biomass. Viable cell numbers were validated by similar correlations between CFU/mL and intracellular DNA content. The intensity of the oxidative burst by neutrophils in response to the fractions was estimated by luminol-enhanced chemiluminescence. At low density, biofilm fractions triggered stronger responses than planktonic cells, whereas at high density, planktonic fractions induced the highest activation, indicating density-dependent modulation. These findings suggest that at low densities, biofilms may exacerbate tissue damage by amplifying neutrophil responses. Therefore, the reduced bacterial load in pwCF on ETI therapy could make the balance between biofilm and planktonic P. aeruginosa more critical for lung inflammation, though their distribution under ETI remains unknown.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 4","pages":"e70210"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687785","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}