William J McCarthy,Frederick Ferguson,Lillian Gelberg
{"title":"For Optimal HIV Viral Load Reduction, Increase Intake of Gut Microbe-Friendly Foods: Comment on Palar et al.","authors":"William J McCarthy,Frederick Ferguson,Lillian Gelberg","doi":"10.1093/infdis/jiaf383","DOIUrl":"https://doi.org/10.1093/infdis/jiaf383","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":"e1060-e1061"},"PeriodicalIF":0.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The United States leads the world in biomedical innovation, with NIH-funded research driving transformative advances in cancer, HIV, and gene therapy. Yet, these breakthroughs cannot achieve their full impact in a fragmented and inequitable health system. Millions remain uninsured, preventive care is undervalued, and social determinants perpetuate life expectancy gaps. Political efforts to restrict or defund the NIH threaten progress and disproportionately harm underserved populations. Biomedical research alone cannot fix systemic failures but strengthening science while repairing care delivery systems is essential to improving population health and ensuring that innovations benefit all.
{"title":"Why Americans are Dying Younger? NIH Is Not the Problem. Our Broken Healthcare Delivery Is.","authors":"Rachel Bender Ignacio,Jade Pagkas-Bather,Gregg Gonsalves,Sara Gianella","doi":"10.1093/infdis/jiaf592","DOIUrl":"https://doi.org/10.1093/infdis/jiaf592","url":null,"abstract":"The United States leads the world in biomedical innovation, with NIH-funded research driving transformative advances in cancer, HIV, and gene therapy. Yet, these breakthroughs cannot achieve their full impact in a fragmented and inequitable health system. Millions remain uninsured, preventive care is undervalued, and social determinants perpetuate life expectancy gaps. Political efforts to restrict or defund the NIH threaten progress and disproportionately harm underserved populations. Biomedical research alone cannot fix systemic failures but strengthening science while repairing care delivery systems is essential to improving population health and ensuring that innovations benefit all.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Sporotrichosis is a chronic, deep fungal infection of skin caused by S.schenckii. Macrophages are predominant in S.schenckii infected skin and able to phagocytize and kill the fungus. Local hyperthermia is effective to treat sporotrichosis, however, its mechanism of action remains not fully understood. Methods Using single-cell RNA sequencing of sporotrichosis lesions, coupled with in vitro and in vivo sporotrichosis models, we investigated the role of TRAF1 and NOS2. Mechanistic studies included co-immunoprecipitation, ubiquitination assays, and site-directed mutagenesis. Therapeutic mechanism of hyperthermia were evaluated in vivo and in vitro. Results We demonstrated for the first time that TRAF1 could delay the healing of sporotrichosis by inhibiting phagocytosis and killing of macrophages to S.schenckii. This effect of TRAF1 is caused by binding NOS2 to regulate its expression and enzymatic activity, through inhibition of NOS2 ubiquitination and subsequent proteasome-induced degradation. Our team's previous research has demonstrated the efficacy of hyperthermia in treating sporotrichosis. Our experiments indicate that hyperthermia can downregulate the expression of TRAF1 and NOS2 in macrophages. Conclusions We identify TRAF1-mediated stabilization of NOS2 as a key immune evasion mechanism in S. schenckii infection. Local hyperthermia represents a targeted therapy against this pathway, offering a novel strategy for enhancing the therapeutic effect of hyperthermia.
{"title":"TRAF1 Inhibits Macrophage Killing of Sporothrix schenckii by Enhancing NOS2 Expression and Activity","authors":"Congcong He, Ruiqun Qi, Yuxiao Hong, Xinghua Gao","doi":"10.1093/infdis/jiaf646","DOIUrl":"https://doi.org/10.1093/infdis/jiaf646","url":null,"abstract":"Background Sporotrichosis is a chronic, deep fungal infection of skin caused by S.schenckii. Macrophages are predominant in S.schenckii infected skin and able to phagocytize and kill the fungus. Local hyperthermia is effective to treat sporotrichosis, however, its mechanism of action remains not fully understood. Methods Using single-cell RNA sequencing of sporotrichosis lesions, coupled with in vitro and in vivo sporotrichosis models, we investigated the role of TRAF1 and NOS2. Mechanistic studies included co-immunoprecipitation, ubiquitination assays, and site-directed mutagenesis. Therapeutic mechanism of hyperthermia were evaluated in vivo and in vitro. Results We demonstrated for the first time that TRAF1 could delay the healing of sporotrichosis by inhibiting phagocytosis and killing of macrophages to S.schenckii. This effect of TRAF1 is caused by binding NOS2 to regulate its expression and enzymatic activity, through inhibition of NOS2 ubiquitination and subsequent proteasome-induced degradation. Our team's previous research has demonstrated the efficacy of hyperthermia in treating sporotrichosis. Our experiments indicate that hyperthermia can downregulate the expression of TRAF1 and NOS2 in macrophages. Conclusions We identify TRAF1-mediated stabilization of NOS2 as a key immune evasion mechanism in S. schenckii infection. Local hyperthermia represents a targeted therapy against this pathway, offering a novel strategy for enhancing the therapeutic effect of hyperthermia.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editor's Note: Oral Ivermectin in the Treatment of Body Lice.","authors":"","doi":"10.1093/infdis/jiaf627","DOIUrl":"https://doi.org/10.1093/infdis/jiaf627","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"155 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruth A Howe, Binayak Rimal, Jay Khandelwal, Chandra Panthi, Gyanu Lamichhane
Background The incidence of non-tuberculous mycobacterial (NTM) infections has been rising and now exceeds tuberculosis in several countries. Mycobacterium avium is the most common NTM cause of chronic lung disease. Current guidelines recommend simultaneous administration of three or more antibiotics, modeled after tuberculosis treatment, but these regimens are limited by toxicity, poor adherence, and low cure rates. Importantly, unlike M. tuberculosis, M. avium is acquired from the environment rather than transmitted between humans, weakening the rationale for multidrug therapy as necessary to suppress resistance. Methods To test an alternative treatment approach, we evaluated sequential monotherapy in a validated murine model of chronic M. avium lung infection. Mice were treated with either the standard triple-drug regimen of clarithromycin, ethambutol, and rifampicin or with sequential monotherapy: clarithromycin, bedaquiline, and clofazimine, with only one drug administered at a time for four-week intervals. Lung and spleen bacterial burdens were quantified, and minimum inhibitory concentrations (MICs) were determined for isolates recovered during treatment to assess resistance emergence. Results Sequential monotherapy achieved reductions in lung bacterial burden equivalent to those of the standard multidrug regimen and prevented extrapulmonary dissemination. Notably, no increase in MICs was observed for clarithromycin, bedaquiline, or clofazimine across treatment phases, indicating that sequential monotherapy did not select for resistant clones. Conclusions These findings provide the first evidence that sequential monotherapy can deliver efficacy comparable to multidrug therapy for M. avium disease without promoting resistance. This proof-of-concept supports further investigation of sequencing strategies as a potentially more tolerable alternative to current triple-agent regimens.
{"title":"Efficacies of sequenced monotherapies of Mycobacterium avium lung infection in mouse","authors":"Ruth A Howe, Binayak Rimal, Jay Khandelwal, Chandra Panthi, Gyanu Lamichhane","doi":"10.1093/infdis/jiaf640","DOIUrl":"https://doi.org/10.1093/infdis/jiaf640","url":null,"abstract":"Background The incidence of non-tuberculous mycobacterial (NTM) infections has been rising and now exceeds tuberculosis in several countries. Mycobacterium avium is the most common NTM cause of chronic lung disease. Current guidelines recommend simultaneous administration of three or more antibiotics, modeled after tuberculosis treatment, but these regimens are limited by toxicity, poor adherence, and low cure rates. Importantly, unlike M. tuberculosis, M. avium is acquired from the environment rather than transmitted between humans, weakening the rationale for multidrug therapy as necessary to suppress resistance. Methods To test an alternative treatment approach, we evaluated sequential monotherapy in a validated murine model of chronic M. avium lung infection. Mice were treated with either the standard triple-drug regimen of clarithromycin, ethambutol, and rifampicin or with sequential monotherapy: clarithromycin, bedaquiline, and clofazimine, with only one drug administered at a time for four-week intervals. Lung and spleen bacterial burdens were quantified, and minimum inhibitory concentrations (MICs) were determined for isolates recovered during treatment to assess resistance emergence. Results Sequential monotherapy achieved reductions in lung bacterial burden equivalent to those of the standard multidrug regimen and prevented extrapulmonary dissemination. Notably, no increase in MICs was observed for clarithromycin, bedaquiline, or clofazimine across treatment phases, indicating that sequential monotherapy did not select for resistant clones. Conclusions These findings provide the first evidence that sequential monotherapy can deliver efficacy comparable to multidrug therapy for M. avium disease without promoting resistance. This proof-of-concept supports further investigation of sequencing strategies as a potentially more tolerable alternative to current triple-agent regimens.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mia Q Zhu,Guillermina Kuan,Hannah E Maier,Roger Lopez,Abigail Shotwell,Miguel Plazaola,Sergio Ojeda,Nery Sanchez,Angel Balmaseda,Aubree Gordon
The role of under-nutrition on influenza virus shedding is unclear. We assessed stunting, an indicator of chronic under-nutrition, as a predictor of shedding duration in children in the Household Influenza Cohort Study, in Managua, Nicaragua. Stunted children, aged 3-9 years, shed influenza longer than their non-stunted peers. In sub-group analysis, associations were driven by H3N2 and influenza B (IB) infections. Analysis of cycle threshold (Ct) values showed slower clearance of IB viruses in stunted children. These findings suggest under-nutrition may prolong influenza shedding, with implications for transmission dynamics and control strategies in low- and middle-income countries where stunting remains prevalent.
{"title":"Stunting Increases Influenza Virus Shedding Duration in Preschool/School-Aged Children.","authors":"Mia Q Zhu,Guillermina Kuan,Hannah E Maier,Roger Lopez,Abigail Shotwell,Miguel Plazaola,Sergio Ojeda,Nery Sanchez,Angel Balmaseda,Aubree Gordon","doi":"10.1093/infdis/jiaf641","DOIUrl":"https://doi.org/10.1093/infdis/jiaf641","url":null,"abstract":"The role of under-nutrition on influenza virus shedding is unclear. We assessed stunting, an indicator of chronic under-nutrition, as a predictor of shedding duration in children in the Household Influenza Cohort Study, in Managua, Nicaragua. Stunted children, aged 3-9 years, shed influenza longer than their non-stunted peers. In sub-group analysis, associations were driven by H3N2 and influenza B (IB) infections. Analysis of cycle threshold (Ct) values showed slower clearance of IB viruses in stunted children. These findings suggest under-nutrition may prolong influenza shedding, with implications for transmission dynamics and control strategies in low- and middle-income countries where stunting remains prevalent.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camille Esneau,David Boettiger,Sarah Leask,Nathan E Bryant,Natalie Niessen,Jodie McVernon,Adrian Marcato,Sandra Carlson,Stuart Browne,Rejoy Thomas,Edward C Holmes,Krispin Hajkowicz,Lynelle Tilbrook,Nathan Moon,Craig Dalton,Nathan W Bartlett,Joshua S Davis
BACKGROUNDThe COVID-19 pandemic has underscored the importance of effective surveillance and early warning systems for respiratory viruses, but most current surveillance data focus on symptomatic individuals visiting healthcare facilities. Symptomatic and asymptomatic virus transmission in the community can both play major roles in the spread of respiratory outbreaks. We aimed to assess the feasibility of monitoring symptomatic and asymptomatic respiratory virus infection in a sample of community dwelling volunteers.METHODSThe Pandemic REspiratory Virus Epidemiological SurveillaNce Trial (PREVENT) was nested within the ongoing FluTracking platform, which involves community-dwelling adults filling in a weekly online respiratory symptom survey. We recruited 52 FluTracking participants living in one Australian city to self-collect weekly nasal swabs and return them via post for a 50-week period. All swabs were tested for the presence of respiratory viruses using a 16-plex PCR panel. Results were correlated with weekly symptom surveys.RESULTSA total of 2,068 nasal swabs were received, corresponding to an 84% swab collection and return rate. 55 samples (3.0%) were discarded due to delayed postage or sample leakage. At least one sample tested positive for virus in 231 of 2,013 participant-weeks (11.0%), with 24.2% of these detections being in asymptomatic individuals. Rhinovirus (57.6% of positive swabs) and SARS-COV-2 (20.3% of positive swabs) were the most frequently detected viruses.CONCLUSIONRegular self-collected nasal swabs for detecting respiratory viruses in a community setting is feasible in Australia and provides valuable information on asymptomatic infection.
{"title":"The Pandemic REspiratory Virus Epidemiological SurveillaNce Trial - A self-swab surveillance system for respiratory viruses nested within FluTracking.","authors":"Camille Esneau,David Boettiger,Sarah Leask,Nathan E Bryant,Natalie Niessen,Jodie McVernon,Adrian Marcato,Sandra Carlson,Stuart Browne,Rejoy Thomas,Edward C Holmes,Krispin Hajkowicz,Lynelle Tilbrook,Nathan Moon,Craig Dalton,Nathan W Bartlett,Joshua S Davis","doi":"10.1093/infdis/jiaf632","DOIUrl":"https://doi.org/10.1093/infdis/jiaf632","url":null,"abstract":"BACKGROUNDThe COVID-19 pandemic has underscored the importance of effective surveillance and early warning systems for respiratory viruses, but most current surveillance data focus on symptomatic individuals visiting healthcare facilities. Symptomatic and asymptomatic virus transmission in the community can both play major roles in the spread of respiratory outbreaks. We aimed to assess the feasibility of monitoring symptomatic and asymptomatic respiratory virus infection in a sample of community dwelling volunteers.METHODSThe Pandemic REspiratory Virus Epidemiological SurveillaNce Trial (PREVENT) was nested within the ongoing FluTracking platform, which involves community-dwelling adults filling in a weekly online respiratory symptom survey. We recruited 52 FluTracking participants living in one Australian city to self-collect weekly nasal swabs and return them via post for a 50-week period. All swabs were tested for the presence of respiratory viruses using a 16-plex PCR panel. Results were correlated with weekly symptom surveys.RESULTSA total of 2,068 nasal swabs were received, corresponding to an 84% swab collection and return rate. 55 samples (3.0%) were discarded due to delayed postage or sample leakage. At least one sample tested positive for virus in 231 of 2,013 participant-weeks (11.0%), with 24.2% of these detections being in asymptomatic individuals. Rhinovirus (57.6% of positive swabs) and SARS-COV-2 (20.3% of positive swabs) were the most frequently detected viruses.CONCLUSIONRegular self-collected nasal swabs for detecting respiratory viruses in a community setting is feasible in Australia and provides valuable information on asymptomatic infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina S Thornton,Drake C Bouzek,Lindsay J Caverly
Cystic fibrosis (CF) lung disease is a result of defective CFTR-mediated ion transport, producing dehydrated mucus, impaired mucociliary clearance and an opportune environment for chronic airway infection. CF airway infections are polymicrobial airway ecosystems often dominated by CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia, Stenotrophomonas, Achromobacter, and nontuberculous mycobacteria that drive cycles of infection, inflammation, and bronchiectasis. Highly effective CFTR modulators, including elexacaftor/tezacaftor/ivacaftor, improve airway hydration and mucociliary clearance and reduce pathogen CF acquisition and density. However, even with CFTR modulator treatment, most individuals with established infection remain chronically infected, and long-term impacts of CFTR modulators on airway infection dynamics and associated clinical outcomes remain unclear. In this review, we address key gaps in understanding chronic infection in the CFTR modulator era, including changes in infection-related lung disease pathogenesis, airway-gut microbiome interactions, approaches to airway infection sampling, and implications for infection management.
{"title":"Microbiota, Mucus, and Modulators: CF Infection Pathogenesis in the CFTR Modulator Era.","authors":"Christina S Thornton,Drake C Bouzek,Lindsay J Caverly","doi":"10.1093/infdis/jiaf626","DOIUrl":"https://doi.org/10.1093/infdis/jiaf626","url":null,"abstract":"Cystic fibrosis (CF) lung disease is a result of defective CFTR-mediated ion transport, producing dehydrated mucus, impaired mucociliary clearance and an opportune environment for chronic airway infection. CF airway infections are polymicrobial airway ecosystems often dominated by CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia, Stenotrophomonas, Achromobacter, and nontuberculous mycobacteria that drive cycles of infection, inflammation, and bronchiectasis. Highly effective CFTR modulators, including elexacaftor/tezacaftor/ivacaftor, improve airway hydration and mucociliary clearance and reduce pathogen CF acquisition and density. However, even with CFTR modulator treatment, most individuals with established infection remain chronically infected, and long-term impacts of CFTR modulators on airway infection dynamics and associated clinical outcomes remain unclear. In this review, we address key gaps in understanding chronic infection in the CFTR modulator era, including changes in infection-related lung disease pathogenesis, airway-gut microbiome interactions, approaches to airway infection sampling, and implications for infection management.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziyi Wang, Nelly Amenyogbe, Rym Ben-Othman, Bing Cai, Mandy Lo, Olubukola T Idoko, Oludare A Odumade, Reza Falsafi, Travis M Blimkie, Andy An, Casey P Shannon, Sebastiano Montante, Bhavjinder K Dhillon, Joann Diray-Arce, Al Ozonoff, Kinga K Smolen, Ryan R Brinkman, Kerry McEnaney, Asimenia Angelidou, Peter Richmond, Scott J Tebbutt, Beate Kampmann, Robert E W Hancock, Amy H Y Lee, Ofer Levy, Tobias R Kollmann, David Martino
We investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes and immune cell counts from the EPIC-HIPC newborn cohort, we report promoter methylation was negatively correlated (Pearson's r = -0.5, p < 2.2×10-16) with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. Higher promoter methylation at birth was associated with lower UBASH3A expression and reduced early onset sepsis risk (OR = 0.26, p = 0.015). Genetic variation significantly influenced variations in baseline UBASH3A methylation (132 cis-meQTL, FDR < 0.05).
我们研究了UBASH3A基因的遗传和表观遗传调控及其与早发性脓毒症的关系。通过对EPIC-HIPC新生儿队列的匹配全血DNA甲基化、基因表达、基因型和免疫细胞计数，我们报告启动子甲基化与UBASH3A基因表达和循环CD3+ t细胞数量的个体发生变化呈负相关（Pearson's r = -0.5, p < 2.2×10-16）。出生时较高的启动子甲基化与较低的UBASH3A表达和较低的早期脓毒症风险相关（OR = 0.26, p = 0.015）。遗传变异显著影响基线UBASH3A甲基化的变化（132顺式- meqtl， FDR < 0.05）。
{"title":"Higher promoter methylation of the Ubiquitin Associated and SH3 domain containing A ( UBASH3A ) gene is associated with T-lymphocyte ontogeny and reduced susceptibility to early-onset sepsis","authors":"Ziyi Wang, Nelly Amenyogbe, Rym Ben-Othman, Bing Cai, Mandy Lo, Olubukola T Idoko, Oludare A Odumade, Reza Falsafi, Travis M Blimkie, Andy An, Casey P Shannon, Sebastiano Montante, Bhavjinder K Dhillon, Joann Diray-Arce, Al Ozonoff, Kinga K Smolen, Ryan R Brinkman, Kerry McEnaney, Asimenia Angelidou, Peter Richmond, Scott J Tebbutt, Beate Kampmann, Robert E W Hancock, Amy H Y Lee, Ofer Levy, Tobias R Kollmann, David Martino","doi":"10.1093/infdis/jiaf636","DOIUrl":"https://doi.org/10.1093/infdis/jiaf636","url":null,"abstract":"We investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes and immune cell counts from the EPIC-HIPC newborn cohort, we report promoter methylation was negatively correlated (Pearson's r = -0.5, p &lt; 2.2×10-16) with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. Higher promoter methylation at birth was associated with lower UBASH3A expression and reduced early onset sepsis risk (OR = 0.26, p = 0.015). Genetic variation significantly influenced variations in baseline UBASH3A methylation (132 cis-meQTL, FDR &lt; 0.05).","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：