The Journal of Infectious Diseases最新文献

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Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis 人类病毒感染和细菌败血症病例中神经损伤血液生物标志物的回顾性分析
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae445
Maggie L Bartlett, Heather Goux, Linwood Johnson, Kevin L Schully, Melissa Gregory, Joost Brandsma, Josh G Chenoweth, Danielle V Clark, Luis Felipe Rivera, Carlos Lezcano-Coba, Amy Y Vittor, Ronald Hayes, Josefrancisco Galué, Jean-Paul Carrera, Darci R Smith
{"title":"Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis","authors":"Maggie L Bartlett, Heather Goux, Linwood Johnson, Kevin L Schully, Melissa Gregory, Joost Brandsma, Josh G Chenoweth, Danielle V Clark, Luis Felipe Rivera, Carlos Lezcano-Coba, Amy Y Vittor, Ronald Hayes, Josefrancisco Galué, Jean-Paul Carrera, Darci R Smith","doi":"10.1093/infdis/jiae445","DOIUrl":"https://doi.org/10.1093/infdis/jiae445","url":null,"abstract":"Background Blood biomarkers of neurological injury could provide a rapid diagnosis of central nervous system (CNS) injury caused by infections. An FDA-approved assay for mild traumatic brain injury (TBI) measures glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), which signal astrocyte and neuronal injury, respectively. Here, we assessed the applicability of this biomarker assay for determining infection-induced brain injury. Methods We measured serum levels of GFAP and UCH-L1 retrospectively in serum samples from three study populations: 1) human cases infected with Venezuelan equine encephalitis virus (VEEV) and Madariaga virus (MADV) (n = 73), 2) human sepsis patients who were severely ill or diagnosed with encephalitis (n = 66), and 3) sepsis cases that were subsequently evaluated for cognitive impairment (n = 64). Results In the virus infection group, we found elevated GFAP for VEEV (p = 0.014) and MADV (p = 0.011) infections, which correlated with seizures (p = 0.006). In the bacterial sepsis group, GFAP was elevated in cases diagnosed with encephalitis (p = 0.0007) and correlated with headaches (p = 0.0002). In the bacterial sepsis cases with a later cognitive assessment, elevated GFAP (p = 0.0057) at study enrollment was associated with cognitive impairment six months later with a positive prognostic capacity of 79% (CI: 66–95%; p = 0.0068). Conclusions GFAP and UCH-L1 levels measured using an FDA-approved assay for TBI may indicate brain injury resulting from viral or bacterial infections and could predict the development of neurological sequelae.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166639","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}
引用次数: 0
Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome. 阿尔茨海默病起源于生命早期微生物群紊乱
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae200
Stephen D Ginsberg,Martin J Blaser
{"title":"Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.","authors":"Stephen D Ginsberg,Martin J Blaser","doi":"10.1093/infdis/jiae200","DOIUrl":"https://doi.org/10.1093/infdis/jiae200","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170678","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}
引用次数: 0
An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice. 肠道细菌感染引发 3xTg-AD 转基因小鼠神经炎症和神经行为障碍
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae165
Gwoncheol Park,Saurabh Kadyan,Nathaniel Hochuli,Gloria Salazar,Orlando Laitano,Paramita Chakrabarty,Philip A Efron,M Ammar Zafar,Aaron Wilber,Ravinder Nagpal
{"title":"An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice.","authors":"Gwoncheol Park,Saurabh Kadyan,Nathaniel Hochuli,Gloria Salazar,Orlando Laitano,Paramita Chakrabarty,Philip A Efron,M Ammar Zafar,Aaron Wilber,Ravinder Nagpal","doi":"10.1093/infdis/jiae165","DOIUrl":"https://doi.org/10.1093/infdis/jiae165","url":null,"abstract":"BACKGROUNDKlebsiella pneumoniae is infamous for hospital-acquired infections and sepsis, which have also been linked to Alzheimer disease (AD)-related neuroinflammatory and neurodegenerative impairment. However, its causative and mechanistic role in AD pathology remains unstudied.METHODSA preclinical model of K. pneumoniae enteric infection and colonization is developed in an AD model (3xTg-AD mice) to investigate whether and how K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis.RESULTSK. pneumoniae, particularly under antibiotic-induced dysbiosis, was able to translocate from the gut to the bloodstream by penetrating the gut epithelial barrier. Subsequently, K. pneumoniae infiltrated the brain by breaching the blood-brain barrier. Significant neuroinflammatory phenotype was observed in mice with K. pneumoniae brain infection. K. pneumoniae-infected mice also exhibited impaired neurobehavioral function and elevated total tau levels in the brain. Metagenomic analyses revealed an inverse correlation of K. pneumoniae with gut biome diversity and commensal bacteria, highlighting how antibiotic-induced dysbiosis triggers an enteroseptic \"pathobiome\" signature implicated in gut-brain perturbations.CONCLUSIONSThe findings demonstrate how infectious agents following hospital-acquired infections and consequent antibiotic regimen may induce gut dysbiosis and pathobiome and increase the risk of sepsis, thereby increasing the predisposition to neuroinflammatory and neurobehavioral impairments via breaching the gut-blood-brain barrier.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170676","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}
引用次数: 0
Bacterial Membrane Vesicles: The Missing Link Between Bacterial Infection and Alzheimer Disease. 细菌膜泡:细菌感染与阿尔茨海默病之间缺失的联系
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae228
Catherine A Butler,Giuseppe D Ciccotosto,Nathaniel Rygh,Elly Bijlsma,Stuart G Dashper,Angela C Brown
{"title":"Bacterial Membrane Vesicles: The Missing Link Between Bacterial Infection and Alzheimer Disease.","authors":"Catherine A Butler,Giuseppe D Ciccotosto,Nathaniel Rygh,Elly Bijlsma,Stuart G Dashper,Angela C Brown","doi":"10.1093/infdis/jiae228","DOIUrl":"https://doi.org/10.1093/infdis/jiae228","url":null,"abstract":"Periodontitis is a common chronic inflammatory disease, affecting approximately 19% of the global adult population. A relationship between periodontal disease and Alzheimer disease has long been recognized, and recent evidence has been uncovered to link these 2 diseases mechanistically. Periodontitis is caused by dysbiosis in the subgingival plaque microbiome, with a pronounced shift in the oral microbiota from one consisting primarily of Gram-positive aerobic bacteria to one predominated by Gram-negative anaerobes, such as Porphyromonas gingivalis. A common phenomenon shared by all bacteria is the release of membrane vesicles to facilitate biomolecule delivery across long distances. In particular, the vesicles released by P gingivalis and other oral pathogens have been found to transport bacterial components across the blood-brain barrier, initiating the physiologic changes involved in Alzheimer disease. In this review, we summarize recent data that support the relationship between vesicles secreted by periodontal pathogens to Alzheimer disease pathology.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170677","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}
引用次数: 0
COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children COVID-19 mRNA 疫苗可在幼儿口咽部诱导大量 IgG,但诱导的 IgA 数量有限
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae450
Ying Tang, Brittany P Boribong, Zoe N Swank, Melina Demokritou, Maria A F Luban, Alessio Fasano, Michelle Du, Rebecca L Wolf, Joseph Griffiths, John Shultz, Ella Borberg, Sujata Chalise, Wanda I Gonzalez, David R Walt, Lael M Yonker, Bruce H Horwitz
{"title":"COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children","authors":"Ying Tang, Brittany P Boribong, Zoe N Swank, Melina Demokritou, Maria A F Luban, Alessio Fasano, Michelle Du, Rebecca L Wolf, Joseph Griffiths, John Shultz, Ella Borberg, Sujata Chalise, Wanda I Gonzalez, David R Walt, Lael M Yonker, Bruce H Horwitz","doi":"10.1093/infdis/jiae450","DOIUrl":"https://doi.org/10.1093/infdis/jiae450","url":null,"abstract":"Background Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children. Methods We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age (N=24) undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples) or in a convenience sample of children under 5 years of age presenting to pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation. Results Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process. Conclusions Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166638","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}
引用次数: 0
Economic Analyses for Disease Surveillance Planning and Advocacy. 疾病监测规划和宣传的经济分析。
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae444
Lee M Hampton
{"title":"Economic Analyses for Disease Surveillance Planning and Advocacy.","authors":"Lee M Hampton","doi":"10.1093/infdis/jiae444","DOIUrl":"https://doi.org/10.1093/infdis/jiae444","url":null,"abstract":"Public health disease surveillance can guide a range of decisions related to the protection of populations. Economic analysis can be used to assess how surveillance for specific diseases can substitute for or complement other public health interventions and how to structure surveillance most efficiently. Assessing the value and costs of different disease surveillance options as part of broader disease prevention and control efforts is important for both using available resources efficiently to protect populations and communicating the need for additional resources as appropriate.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165953","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}
引用次数: 0
Unveiling the Intricate Link Between Anaerobe Niche and Alzheimer Disease Pathogenesis. 揭示厌氧菌群与阿尔茨海默病发病机制之间的复杂联系
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae312
NyEmma Drakes,Galina Kondrikova,Dariusz Pytel,Eric D Hamlett
{"title":"Unveiling the Intricate Link Between Anaerobe Niche and Alzheimer Disease Pathogenesis.","authors":"NyEmma Drakes,Galina Kondrikova,Dariusz Pytel,Eric D Hamlett","doi":"10.1093/infdis/jiae312","DOIUrl":"https://doi.org/10.1093/infdis/jiae312","url":null,"abstract":"Dysbiosis within microbiomes has been increasingly implicated in many systemic illnesses, such as cardiovascular disease, metabolic syndrome, respiratory infections, and Alzheimer disease (Ad). The correlation between Ad and microbial dysbiosis has been repeatedly shown, yet the etiologic cause of microbial dysbiosis remains elusive. From a neuropathology perspective, abnormal (often age-related) changes in the brain, associated structures, and bodily lumens tend toward an accumulation of oxygen-depleted pathologic structures, which are anaerobically selective niches. These anaerobic environments may promote progressive change in the microbial community proximal to the brain and thus deserve further investigation. In this review, we identify and explore what is known about the anaerobic niche near or associated with the brain and the anaerobes that it is harbors. We identify the anaerobe stakeholders within microbiome communities and the impacts on the neurodegenerative processes associated with Ad. Chronic oral dysbiosis in anaerobic dental pockets and the composition of the gut microbiota from fecal stool are the 2 largest anaerobic niche sources of bacterial transference to the brain. At the blood-brain barrier, cerebral atherosclerotic plaques are predominated by anaerobic species intimately associated with the brain vasculature. Focal cerebritis/brain abscess and corpora amylacea may also establish chronic anaerobic niches in direct proximity to brain parenchyma. In exploring the anaerobic niche proximal to the brain, we identify research opportunities to explore potential sources of microbial dysbiosis associated with Ad.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170679","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}
引用次数: 0
Chronic Oral Inoculation of Porphyromonas gingivalis and Treponema denticola Induce Different Brain Pathologies in a Mouse Model of Alzheimer Disease. 牙龈卟啉单胞菌和齿孢子菌的慢性口腔接种在阿尔茨海默病小鼠模型中诱发不同的脑病理变化
The Journal of Infectious Diseases Pub Date : 2024-09-10 DOI: 10.1093/infdis/jiae286
Giuseppe D Ciccotosto,Ali I Mohammed,Rita Paolini,Elly Bijlsma,Su Toulson,James Holden,Eric C Reynolds,Stuart G Dashper,Catherine A Butler
{"title":"Chronic Oral Inoculation of Porphyromonas gingivalis and Treponema denticola Induce Different Brain Pathologies in a Mouse Model of Alzheimer Disease.","authors":"Giuseppe D Ciccotosto,Ali I Mohammed,Rita Paolini,Elly Bijlsma,Su Toulson,James Holden,Eric C Reynolds,Stuart G Dashper,Catherine A Butler","doi":"10.1093/infdis/jiae286","DOIUrl":"https://doi.org/10.1093/infdis/jiae286","url":null,"abstract":"Periodontitis is a chronic inflammatory disease driven by dysbiosis in subgingival microbial communities leading to increased abundance of a limited number of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Oral health, particularly periodontitis, is a modifiable risk factor for Alzheimer disease (AD) pathogenesis, with components of both these bacteria identified in postmortem brains of persons with AD. Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers. P. gingivalis displays synergistic virulence with T. denticola during periodontitis. The aim of the current study was to determine the ability of P. gingivalis and T. denticola, grown in physiologically relevant conditions, individually and in combination, to induce AD-like pathology following chronic oral inoculation of female mice over 12 weeks. P. gingivalis alone significantly increased all 7 brain pathologies examined: neuronal damage, activation of astrocytes and microglia, expression of inflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 and production of amyloid-β plaques and hyperphosphorylated tau, in the hippocampus, cortex and midbrain, compared to control mice. T. denticola alone significantly increased neuronal damage, activation of astrocytes and microglia, and expression of IL-1β, in the hippocampus, cortex and midbrain, compared to control mice. Coinoculation of P. gingivalis with T. denticola significantly increased activation of astrocytes and microglia in the hippocampus, cortex and midbrain, and increased production of hyperphosphorylated tau and IL-1β in the hippocampus only. The host brain response elicited by oral coinoculation was less than that elicited by each bacterium, suggesting coinoculation was less pathogenic.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170721","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}
引用次数: 0
Role of HLA-B*58:01-restricted CD8+ T cells in HIV-1 subtype AE infection HLA-B*58:01 限制性 CD8+ T 细胞在 HIV-1 亚型 AE 感染中的作用
The Journal of Infectious Diseases Pub Date : 2024-09-09 DOI: 10.1093/infdis/jiae448
Hung The Nguyen, Takayuki Chikata, Yu Zhang, Giang Van Tran, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
{"title":"Role of HLA-B*58:01-restricted CD8+ T cells in HIV-1 subtype AE infection","authors":"Hung The Nguyen, Takayuki Chikata, Yu Zhang, Giang Van Tran, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi","doi":"10.1093/infdis/jiae448","DOIUrl":"https://doi.org/10.1093/infdis/jiae448","url":null,"abstract":"HLA-B*58:01 and HLA-B*57 are protective alleles against HIV-1 subtype B or C infection whereas these HLA alleles have not been reported as protective in HIV-1 subtype AE infection. Although HLA-B*58:01-restricted and HLA-B*57-restricted HIV-1-specific CD8+ T cells have been thoroughly analyzed in subtype B or C infection, they have only been partially analyzed in subtype AE infection. We identified six HLA-B*58:01-restricted subtype AE epitopes in Vietnamese individuals infected with subtype AE. HLA-B*58:01-restricted T-cell responses to Gag epitopes, which may control disease progression in HLA-B*58:01+ and HLA-B*57+ individuals infected with subtype B or C, were not protective in subtype AE infection. These findings suggest that the loss of HLA-B*58:01-restricted T cells specific for some Gag epitopes and/or their reduced ability may account for the lack of protective effects conferred by HLA-B*58:01 in subtype AE infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160461","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}
引用次数: 0
Chlamydia trachomatis induces low-frequency, sustained CD4 T cell responses in most women, predominantly targeting chlamydial protease-like activity factor, CPAF 沙眼衣原体可诱导大多数女性产生低频、持续的 CD4 T 细胞反应,主要针对衣原体蛋白酶样活性因子 CPAF
The Journal of Infectious Diseases Pub Date : 2024-09-09 DOI: 10.1093/infdis/jiae443
Yanli Li, Joanna A Warren, Taylor B Poston, Genevieve Clutton, Fiona R Shaw, Shayla Z Conrad, Yinyan Xu, Xiaojing Zheng, Kacy S Yount, Catherine M O’Connell, Harold C Wiesenfeld, Toni Darville, Nilu Goonetilleke
{"title":"Chlamydia trachomatis induces low-frequency, sustained CD4 T cell responses in most women, predominantly targeting chlamydial protease-like activity factor, CPAF","authors":"Yanli Li, Joanna A Warren, Taylor B Poston, Genevieve Clutton, Fiona R Shaw, Shayla Z Conrad, Yinyan Xu, Xiaojing Zheng, Kacy S Yount, Catherine M O’Connell, Harold C Wiesenfeld, Toni Darville, Nilu Goonetilleke","doi":"10.1093/infdis/jiae443","DOIUrl":"https://doi.org/10.1093/infdis/jiae443","url":null,"abstract":"Background Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection (STI) that can result in pelvic inflammatory disease, ectopic pregnancy and infertility in women. Currently, there is no prophylactic vaccine. Methods This study examined T cell immunity in a cohort of women recently infected with CT. Participants were screened against peptides spanning 33 of 894 possible CT proteins, either ex vivo or using short-term cell lines (STCL). CT-specific T cells were characterized by IFN-γ ELISpot and flow cytometry. Results Ex vivo CT-specific T cells were rarely detected; however, following in vitro expanded CT-specific T cells were detected by IFN-γ ELISpot in 90% (27/30) of participants. Notably, over 50% of participants had T cell responses targeting chlamydial protease-like activity factor (CPAF). T cell epitopes were dispersed across the CPAF protein. Flow cytometry analysis of STCL found CT-specific cells, were mainly CD4+, produced IFN-γ and TNF-α and were sustained over 12 months. Ex vivo analysis suggested CT-specific T cells mostly exhibited a central memory phenotype. Conclusion Our results indicate that CT infection elicits low-frequency, persistent CD4 T cell responses in most women and that the secreted protein, CPAF, is an immunoprevalent CT antigen. Altogether, these data support development and testing of CT vaccines that enhance CD4 T cells against CPAF.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160460","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}
引用次数: 0
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