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Immunity May 2020Tissue-resident memory CD8 T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. Using single-cell RNA-sequencing (scRNA-seq)...
Tissue-resident memory CD8 T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8 T cells, including a Blimp1Id3 tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections and a molecularly distinct Blimp1Id3 tissue-resident memory population that subsequently accumulated at later infection time points. These Trm populations exhibited distinct cytokine production, secondary memory potential, and transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8 T cell populations with tissue-resident gene-expression signatures that shared features of terminally exhausted and progenitor-exhausted T cells, respectively. Our findings provide insight into the development and functional heterogeneity of Trm cells, which has implications for enhancing vaccination and immunotherapy approaches.
Topics: Animals; CD8-Positive T-Lymphocytes; Cells, Cultured; Immunologic Memory; Immunotherapy; Inhibitor of Differentiation Protein 2; Inhibitor of Differentiation Proteins; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neoplasms; Positive Regulatory Domain I-Binding Factor 1
PubMed: 32433949
DOI: 10.1016/j.immuni.2020.04.007 -
Immunity Apr 2023T cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and...
T cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these stem-like CD8 T cells (CD8SL) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection, we identified the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8SL as well as for virus control. IL-33 receptor (ST2)-deficient CD8 T cells exhibited biased end differentiation and premature loss of Tcf-1. ST2-deficient CD8SL responses were restored by blockade of type I interferon signaling, suggesting that IL-33 balances IFN-I effects to control CD8SL formation in chronic infection. IL-33 signals broadly augmented chromatin accessibility in CD8SL and determined these cells' re-expansion potential. Our study identifies the IL-33-ST2 axis as an important CD8SL-promoting pathway in the context of chronic viral infection.
Topics: Animals; Mice; Alarmins; CD8-Positive T-Lymphocytes; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice, Inbred C57BL; Persistent Infection; T Cell Transcription Factor 1
PubMed: 36809763
DOI: 10.1016/j.immuni.2023.01.029 -
The Neurohospitalist Oct 2022As specialists in acute neurology, neurohospitalists are often called upon to diagnose and manage acute viral infections affecting the nervous system. In this broad... (Review)
Review
As specialists in acute neurology, neurohospitalists are often called upon to diagnose and manage acute viral infections affecting the nervous system. In this broad review covering the neurology of several acute viral infections, our aim is to provide key diagnostic and therapeutic pearls of practical use to the busy neurohospitalist. We will review acute presentations, diagnosis, and treatment of human herpesviruses, arboviruses, enteroviruses, and some vaccine-preventable viruses. The neurological effects of coronaviruses, including COVID-19, are not covered in this review.
PubMed: 36147750
DOI: 10.1177/19418744221104778 -
Frontiers in Neurology 2023In recent years, with the rapid development of molecular biology techniques such as polymerase chain reaction and molecular biochip, the etiological diagnosis of viral... (Review)
Review
In recent years, with the rapid development of molecular biology techniques such as polymerase chain reaction and molecular biochip, the etiological diagnosis of viral encephalitis has a very big step forward. At present, the etiological examination of viral meningitis mainly includes virus isolation, serological detection and molecular biological nucleic acid detection. This article reviews the progress in etiological diagnosis of viral meningitis.
PubMed: 37583954
DOI: 10.3389/fneur.2023.1193834 -
Brain : a Journal of Neurology Sep 2023Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide...
Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
Topics: Female; Humans; Adult; Male; Prospective Studies; Prognosis; Meningitis, Viral; Herpesvirus 3, Human
PubMed: 36929167
DOI: 10.1093/brain/awad089 -
Microbial Genomics Aug 2023Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly...
Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly advanced our understanding of the viruses responsible for these diseases. However, the detection rate of the aetiology remains low. We conducted RNA sequencing and virome analysis on cerebrospinal fluid (CSF) and serum samples commonly used in the clinical diagnosis to detect viral pathogens. In total, 226 paired CSF and serum samples from 113 children with encephalitis and meningitis were enrolled. The results showed that the diversity of viruses was higher in CSF, with a total of 12 viral taxa detected, including one case each of herpesvirus, coronavirus and enterovirus, and six cases of adenovirus related to human diseases. In contrast, the was the most abundant viral family detected in serum, and only a few samples contained human viral pathogens, including one case of enterovirus and two cases of adenovirus. The detection rate for human viral pathogens increases to 10.6 %(12/113) when both types of samples are used simultaneously, compared to CSF along 7.9 % (9/113) or serum alone 2.6 % (3/113). However, we did not detect these viruses simultaneously in paired samples from the same case. These results suggest that CSF samples still have irreplaceable advantages for using mNGS to detect viruses in patients with meningitis and encephalitis, and serum can supplement to improve the detection rate of viral encephalitis and meningitis. The findings of this study could help improve the etiological diagnosis, clinical management and prognosis of patients with meningitis and encephalitis in children.
Topics: Infant; Humans; Child; Meningitis; Encephalitis; Viruses; Enterovirus; Sequence Analysis, RNA; RNA
PubMed: 37531160
DOI: 10.1099/mgen.0.001079 -
Journal of Neurovirology Aug 2020Seven coronavirus (CoV) species are known human pathogens: the epidemic viruses SARS-CoV, SARS-CoV-2, and MERS-CoV and those continuously circulating in human... (Review)
Review
Seven coronavirus (CoV) species are known human pathogens: the epidemic viruses SARS-CoV, SARS-CoV-2, and MERS-CoV and those continuously circulating in human populations since initial isolation: HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63. All have associations with human central nervous system (CNS) dysfunction. In infants and young children, the most common CNS phenomena are febrile seizures; in adults, non-focal abnormalities that may be either neurologic or constitutional. Neurotropism and neurovirulence are dependent in part on CNS expression of cell surface receptors mediating viral entry, and host immune response. In adults, CNS receptors for epidemic viruses are largely expressed on brain vasculature, whereas receptors for less pathogenic viruses are present in vasculature, brain parenchyma, and olfactory neuroepithelium, dependent upon viral species. Human coronaviruses can infect circulating mononuclear cells, but meningoencephalitis is rare. Well-documented human neuropathologies are infrequent and, for SARS, MERS, and COVID-19, can entail cerebrovascular accidents originating extrinsically to brain. There is evidence of neuronal infection in the absence of inflammatory infiltrates with SARS-CoV, and CSF studies of rare patients with seizures have demonstrated virus but no pleocytosis. In contrast to human disease, animal models of neuropathogenesis are well developed, and pathologies including demyelination, neuronal necrosis, and meningoencephalitis are seen with both native CoVs as well as human CoVs inoculated into nasal cavities or brain. This review covers basic CoV biology pertinent to CNS disease; the spectrum of clinical abnormalities encountered in infants, children, and adults; and the evidence for CoV infection of human brain, with reference to pertinent animal models of neuropathogenesis.
Topics: Animals; Betacoronavirus; COVID-19; Coronaviridae; Coronaviridae Infections; Coronavirus Infections; Humans; Meningitis, Viral; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32737861
DOI: 10.1007/s13365-020-00868-7 -
The Journal of Infection Mar 2024Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to... (Review)
Review
Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.
Topics: Humans; Proteomics; Diagnosis, Differential; Meningitis, Viral; Biomarkers; Meningitis, Bacterial; Anti-Bacterial Agents
PubMed: 38307149
DOI: 10.1016/j.jinf.2024.01.010 -
Frontiers in Cellular and Infection... 2023Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM).
INTRODUCTION
Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM).
METHODS
In our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data.
RESULTS
Ten viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired.
DISCUSSION
Our result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns.
Topics: Humans; Child; Proteomics; Encephalitis, Viral; Viruses; Meningitis, Viral; Enterovirus; High-Throughput Nucleotide Sequencing; Metagenomics; Sensitivity and Specificity
PubMed: 37153144
DOI: 10.3389/fcimb.2023.1104858 -
Frontiers in Public Health 2022The comprehensive epidemiology and impact of climate on viral meningitis (VM) in Kazakhstan are unknown. We aimed to study the incidence, in-hospital mortality and...
BACKGROUND
The comprehensive epidemiology and impact of climate on viral meningitis (VM) in Kazakhstan are unknown. We aimed to study the incidence, in-hospital mortality and influence of climatic indicators on VM from 2014 to 2019.
METHODS
Nationwide electronic healthcare records were used to explore this study. ICD-10 codes of VM, demographics, and hospital outcomes were evaluated using descriptive statistics and survival analysis.
RESULTS
During the 2014-2019 period, 10,251 patients with VM were admitted to the hospital. 51.35% of them were children, 57.85% were males, and 85.9% were from the urban population. Enteroviral meningitis was the main cause of VM in children. The incidence rate was 13 and 18 cases per 100,000 population in 2014 and 2019, respectively. Case fatality rate was higher in 2015 (2.3%) and 2017 (2.0%). The regression model showed 1°C increment in the daily average temperature might be associated with a 1.05-fold (95% CI 1.047-1.051) increase in the daily rate of VM cases, 1hPa increment in the average air pressure and 1% increment in the daily average humidity might contribute to a decrease in the daily rate of VM cases with IRRs of 0.997 (95% CI 0.995-0.998) and 0.982 (95% CI 0.981-0.983), respectively. In-hospital mortality was 35% higher in males compared to females. Patients residing in rural locations had a 2-fold higher risk of in-hospital death, compared to city residents. Elderly patients had a 14-fold higher risk of in-hospital mortality, compared to younger patients.
CONCLUSION
This is the first study in Kazakhstan investigating the epidemiology and impact of climate on VM using nationwide healthcare data. There was a tendency to decrease the incidence with outbreaks every 5 years, and mortality rates were higher for Russians and other ethnicities compared to Kazakhs, for males compared to females, for elder patients compared to younger patients, and for patients living in rural areas compared to city residents. The climatic parameters and the days of delay indicated a moderate interaction with the VM cases.
Topics: Male; Child; Female; Humans; Aged; Hospital Mortality; Kazakhstan; Meningitis, Viral; Incidence; Russia
PubMed: 36684964
DOI: 10.3389/fpubh.2022.1041135