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Journal of Visualized Experiments : JoVE Apr 2024Follicular Helper T (TFH) cells are perceived as an independent CD4 T cell lineage that assists cognate B cells in producing high-affinity antibodies, thus establishing...
Follicular Helper T (TFH) cells are perceived as an independent CD4 T cell lineage that assists cognate B cells in producing high-affinity antibodies, thus establishing long-term humoral immunity. During acute viral infection, the fate commitment of virus-specific TFH cells is determined in the early infection phase, and investigations of the early-differentiated TFH cells are crucial in understanding T cell-dependent humoral immunity and optimizing vaccine design. In the study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection and the TCR-transgenic SMARTA (SM) mouse with CD4 T cells specifically recognizing LCMV glycoprotein epitope I-AGP66-77, we described procedures to access the early fate commitment of virus-specific TFH cells based on flow cytometry stainings. Furthermore, by exploiting retroviral transduction of SM CD4 T cells, methods to manipulate gene expression in early-differentiated virus-specific TFH cells are also provided. Hence, these methods will help in studies exploring the mechanism(s) underlying the early commitment of virus-specific TFH cells.
Topics: Animals; Mice; CD4-Positive T-Lymphocytes; Cell Differentiation; Flow Cytometry; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice, Inbred C57BL; Mice, Transgenic; T Follicular Helper Cells; T-Lymphocytes, Helper-Inducer
PubMed: 38738889
DOI: 10.3791/66752 -
Vector Borne and Zoonotic Diseases... May 2024Chikungunya is a zoonotic disease caused by the Chikungunya virus (CHIKV), primarily transmitted to humans through infected Aedes mosquitoes. The infection is...
Chikungunya is a zoonotic disease caused by the Chikungunya virus (CHIKV), primarily transmitted to humans through infected Aedes mosquitoes. The infection is characterized by symptoms such as high fever, musculoskeletal pain, polyarthritis, and a rash, which can lead to severe complications such as encephalitis, meningitis, and even fatalities. While many disease manifestations resemble those of other viral infections, chronic arthritis caused by CHIKV is unique, and its molecular mechanisms remain ill-defined. Proteomics data from both cellular and patient levels of CHIKV infection were curated from PubMed and screened using inclusion and exclusion criteria. Patient serum proteomics data obtained from PRIDE underwent reanalysis using Proteome Discoverer 2.2. Enrichment and protein-protein interaction network analysis were conducted on differentially expressed proteins from both serum and cellular datasets. Metabolite data from CHIKV-infected patients were further retrieved, and their protein binding partners were identified using BindingDB. The protein-metabolite interaction pathway was further developed using MetaboAnalyst. The proteomics data analysis revealed differential expression of proteins involved in critical host mechanisms, such as cholesterol metabolism and mRNA splicing, during CHIKV infection. Consistent upregulation of two actin cytoskeleton proteins, TAGLN2 and PFN1, was noted in both serum and cellular datasets, and their upregulations are associated with arthritis. Furthermore, alterations in purine metabolism were observed in the integrative proteome-metabolome analysis, correlating with cytoskeletal remodelling. Collectively, this integrative view sheds light on the involvement of actin cytoskeleton remodeling proteins and purine metabolic pathways in the development of arthritis during CHIKV infection.
PubMed: 38717066
DOI: 10.1089/vbz.2024.0018 -
Zhonghua Nei Ke Za Zhi May 2024The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome... (Review)
Review
The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome and Epstein-Barr Virus (EBV) positive cerebrospinal fluid, as detected through metagenomic next-generation sequencing (mNGS). It reviews existing literature to examine the connections between EBV and various conditions including Sjogren's syndrome, encephalitis or meningitis, and nasopharyngeal carcinoma, emphasizing the importance of EBV positive cerebrospinal fluid. The study focuses on a case from the Eighth Medical Center of the General Hospital of the People's Liberation Army, where a patient was admitted with headaches as the primary symptom on March 3, 2021. This patient had a history of Sjogren's syndrome and was later diagnosed with nasopharyngeal carcinoma. The research involved reviewing both domestic and international databases for cases related to cerebrospinal fluid EBV positive encephalitis or meningitis, and nasopharyngeal carcinoma. It aimed to aggregate data on demographics, initial symptoms, treatment methods, and patient outcomes. Findings suggest that positive cerebrospinal fluid EBV is linked to autoimmune diseases, viral encephalitis or meningitis, and nasopharyngeal carcinoma, albeit infrequently in the context of Sjogren's syndrome. Notably, EBV positive cerebrospinal fluid is commonly associated with recurrent nasopharyngeal carcinoma rather than initial episodes. The study concludes that for patients with an immune condition, exhibiting symptoms like headaches or cranial nerve issues, or in cases where nasopharyngeal carcinoma is suspected, early testing through cerebrospinal fluid mNGS or EBV DNA is recommended. This approach facilitates risk assessment, prognosis determination, and the creation of individualized treatment plans.
Topics: Humans; Sjogren's Syndrome; Nasopharyngeal Carcinoma; Herpesvirus 4, Human; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections; High-Throughput Nucleotide Sequencing
PubMed: 38715487
DOI: 10.3760/cma.j.cn112138-20231110-00311 -
Medical Mycology May 2024Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus...
Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.
Topics: Humans; Meningitis, Cryptococcal; Male; Female; Retrospective Studies; Adult; Middle Aged; Herpesvirus 4, Human; DNA, Viral; Epstein-Barr Virus Infections; Aged; Cerebrospinal Fluid; Cryptococcus neoformans; High-Throughput Nucleotide Sequencing; Metagenomics; Young Adult; China; Survival Analysis
PubMed: 38710585
DOI: 10.1093/mmy/myae052 -
Heliyon May 2024Acute meningitis is a disease with case fatality and disability rate that is dependent on the causative agent.
BACKGROUND
Acute meningitis is a disease with case fatality and disability rate that is dependent on the causative agent.
OBJECTIVE
Determine the meningitis trend in Iraq from 2007 to 2023 using a joinpoint regression at national and sub-national levels and describe the epidemiology.
METHODS
Joinpoint regression model was used on surveillance data from Jan 2007 until May 2023, to calculate annual and average annual percent changes to determine the trend. Meningitis total count was modelled by year of reporting and province using the log transformation and Poisson variance. Best-fit model was chosen based on the weighted BIC criteria as the final point.
RESULTS
Bacterial meningitis was higher than viral meningitis from 2007 to 2018, then viral meningitis started to exceed till 2023. Meningococcal meningitis was lower than other bacterial and viral meningitis from 2007 to 2023. Most meningitis cases across the years were lower than 15 years, at almost 80 %, while 20 %-40 % were lower than one year. Across all years, 55 % of the cases were males; apart from 2019, 70 % were females.
CONCLUSION
In Iraq, viral meningitis has been the predominant type since 2018. Most meningitis patients were lower than 15-year-old males. The meningitis trend in Iraq was stable from 2007 till 2023.
PubMed: 38707473
DOI: 10.1016/j.heliyon.2024.e30088 -
Heliyon Apr 2024Central nervous system (CNS) tuberculosis is a post-primary form of tuberculosis. It has high mortality and morbidity rates despite early diagnosis and treatment. CNS... (Review)
Review
Central nervous system (CNS) tuberculosis is a post-primary form of tuberculosis. It has high mortality and morbidity rates despite early diagnosis and treatment. CNS tuberculosis can manifest as subacute/chronic meningitis, parenchymal tuberculous lesions, and spinal tuberculosis. Hematogenous spread of tuberculous bacilli to the brain results in the development of so called "rich foci" on the pial surface, ependyma, and grey-white matter junction. Rupture of these "rich foci" into the subarachnoid space triggers an intense granulomatous inflammatory reaction. Tuberculous meningitis can manifest as leptomeningitis or pachymeningitis. Intracranial parenchymal tuberculous lesions may present as tuberculoma, tuberculous abscess, cerebritis, rhombencephalitis, and encephalopathy, with atypical presentations not uncommon. Complications of CNS tuberculosis encompass hydrocephalus, syrinx formation, vasculitis, infarcts, neuritis, and enduring neurological deficits. Post-contrast 3D fluid-attenuated inversion recovery (FLAIR) and post-contrast T1 spin-echo sequences excel in detecting tuberculous meningitis compared to other conventional magnetic resonance imaging (MRI) sequences. In proton magnetic resonance spectroscopy (PMRS), the presence of a lipid peak at 1.3 ppm is indicative of tuberculous lesions. Magnetization transfer (MT) imaging enhances the detection of tuberculous lesions, as the magnetization transfer ratio (MTR) of tuberculous pathologies, owing to their high lipid content, is lower than that in bacterial or fungal pathologies and higher than that in viral pathologies. This review article delves into the various typical and atypical imaging presentations of CNS tuberculosis in MRI, along with recent advances in imaging techniques.
PubMed: 38699716
DOI: 10.1016/j.heliyon.2024.e29779 -
Virology Journal May 2024Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like...
Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection.
Topics: Humans; Female; Middle Aged; Immunocompromised Host; Picornaviridae Infections; Parechovirus; Saudi Arabia; High-Throughput Nucleotide Sequencing; Glioblastoma; Metagenomics; Encephalitis, Viral; Herpesvirus 1, Human; Hospitalization
PubMed: 38698421
DOI: 10.1186/s12985-024-02372-4 -
Frontiers in Medicine 2024The Biofire FilmArray Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide....
BACKGROUND
The Biofire FilmArray Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule.
MATERIALS
Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests.
RESULTS
1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria.
CONCLUSION
The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.
PubMed: 38695026
DOI: 10.3389/fmed.2024.1351903 -
Cureus Mar 2024Drug-induced aseptic meningitis is a rare condition that occurs because of an adverse reaction to medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and...
Drug-induced aseptic meningitis is a rare condition that occurs because of an adverse reaction to medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Unlike bacterial or viral meningitis, aseptic meningitis is not caused by an infection, but rather by an inflammatory response. This condition creates a challenge since patients with aseptic meningitis often present with classic clinical meningeal symptoms, including fever, headache, and neck stiffness. We present a case of a patient with NSAID-induced aseptic meningitis and highlight the importance for healthcare providers to have a high index of suspicion for drug-induced aseptic meningitis in patients presenting with symptoms of meningitis with negative cerebrospinal fluid analysis and culture.
PubMed: 38690497
DOI: 10.7759/cureus.57349 -
Cell Reports May 2024The maintenance of antigen-specific CD8 T cells underlies the efficacy of vaccines and immunotherapies. Pathways contributing to CD8 T cell loss are not completely...
The maintenance of antigen-specific CD8 T cells underlies the efficacy of vaccines and immunotherapies. Pathways contributing to CD8 T cell loss are not completely understood. Uncovering the pathways underlying the limited persistence of CD8 T cells would be of significant benefit for developing novel strategies of promoting T cell persistence. Here, we demonstrate that murine CD8 T cells experience endoplasmic reticulum (ER) stress following activation and that the ER-associated degradation (ERAD) adapter Sel1L is induced in activated CD8 T cells. Sel1L loss limits CD8 T cell function and memory formation following acute viral infection. Mechanistically, Sel1L is required for optimal bioenergetics and c-Myc expression. Finally, we demonstrate that human CD8 T cells experience ER stress upon activation and that ER stress is negatively associated with improved T cell functionality in T cell-redirecting therapies. Together, these results demonstrate that ER stress and ERAD are important regulators of T cell function and persistence.
Topics: Animals; Humans; Mice; Acute Disease; CD8-Positive T-Lymphocytes; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Immunologic Memory; Intracellular Signaling Peptides and Proteins; Lymphocytic Choriomeningitis; Mice, Inbred C57BL; Proteins; RNA-Binding Proteins; Male; Female
PubMed: 38687642
DOI: 10.1016/j.celrep.2024.114156