Increased Frequency of Tim-3 Expressing T Cells Is Associated with Symptomatic West Nile Virus Infection

Lanteri, Marion C.; Diamond, Michael S.; Law, Jacqueline; Chew, Glen M.; Wu, Shiquan; Inglis, Heather C.; Wong, Derek P.; Busch, Michael P.; Norris, Philip J.; Ndhlovu, Lishomwa C.

doi:10.1371/journal.pone.0092134

Cited by 17 publications

(19 citation statements)

References 32 publications

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“…Of note, subjects with a history of severe disease had lower levels of plasmacytoid DCs (pDCs) (CD123 ϩ ) (P Ͻ 0.05), which are critical for antiviral responses. In the profiling of T cells, severely infected subjects showed elevated levels of regulatory T cells (P Ͻ 0.01), although these cells were previously shown to have a protective role in acute infection in murine models and in acute asymptomatic WNV patients and patients with mild WNV infection (possibly mediated by Tim3 ϩ Tregs [31,32]). Although these individual subset differences did not remain significant after correcting for multiplehypothesis testing (FDR Ͼ 0.05), these results raise the possibility that susceptibility to severe disease correlates with an altered PBMC composition.…”

Section: Resultsmentioning

confidence: 97%

Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection

Qian

Goel

Meng

et al. 2014

Clin. Vaccine Immunol.

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West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have integrated systems-level transcriptional and functional data sets from stratified cohorts of subjects with a history of WNV infection to define whether these markers can distinguish susceptibility in a human population. Transcriptional profiles combined with immunophenotyping of primary cells identified a predictive signature of susceptibility that was detectable years after acute infection (67% accuracy), with the most prominent alteration being decreased IL1B induction following ex vivo infection of macrophages with WNV. Deconvolution analysis also determined a significant role for CXCL10 expression in myeloid dendritic cells. This systems analysis identified markers of pathogenic mechanisms and offers insights into potential therapeutic strategies.

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Section: Resultsmentioning

confidence: 97%

Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection

Qian

Goel

Meng

et al. 2014

Clin. Vaccine Immunol.

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“…Symptom questionnaires covering 12 possible WNV-related symptoms (fever, headache, eye pain, body aches, new skin rash, swollen lymph nodes, nausea or vomiting, muscle weakness, confusion, disorientation, memory problems, or other symptom) were administered at study enrollment and two weeks later. As previously described, 37 a cutoff of four symptoms was used to categorized blood donors as asymptomatic (AS, number of reported symptoms < 4, n = 244) or symptomatic (S, number of reported symptoms ≥ 4, n=130) as previously used for pathogenesis studies 10, 14, 38, 39 . The average age was 47.4 years for the WNV+ cohort, 48.2 years for asymptomatic, and 46 for symptomatic WNV+ donors ( P AS vs. S = 0.15) (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Blood group A and D negativity are associated with symptomatic West Nile virus infection

et al. 2016

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Background West Nile virus (WNV) infection is mostly asymptomatic but 20% of subjects report WNV fever and 1% of patients experience neurological diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic infections, it is essential to understand prognostic factors influencing symptomatic disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. The present study investigates the association between the ABO and Rh(D) blood group status and WNV disease outcome. Study Design and Methods The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 asymptomatic (AS) and 130 symptomatic (S) WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O and Rh(D) blood groups and WNV clinical disease outcome. Results Symptomatic WNV+ donors exhibited increased frequencies of blood group A (S 47.6% AS 36.8%, P=0.04, OR [95%CI] 1.56 [1.01–2.40]) and Rh(D)-negative individuals (S 21.5% AS 13.1%, P=0.03, OR [95%CI] 1.82 [1.04–3.18]). Conclusion The findings suggest a genetic susceptibility placing blood group A and Rh(D)-negative individuals at risk for the development of symptomatic disease outcome after WNV infection.

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“…The minor part of pathogenesis can be neurologic deficits and neuroinvasive in elderly people. Viral pathogenesis mainly favours by efferocytosis activator TIM-3, which inhibits CD8 + T cell activation (Lanteri et al 2014). The viral RNA plays major role in dampening the CD8 + T cell activation and it activates CD4 + T cell expresses Th1 and Th17 cytokines that favours neuroinvasion (James et al 2016).…”

Section: T Cell Responses In West Nile Virusmentioning

confidence: 99%

T Cells in Viral Infections: The Myriad Flavours of Antiviral Immunity

Jagadeesh

Prathyusha

Sheela

et al. 2020

Dynamics of Immune Activation in Viral Diseases

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Viral diseases are a major cause of morbidity and mortality and result in a significant public health burden. T lymphocytes first identified in the chordate lineage and constitute a highly sophisticated branch of adaptive immune system. Apart from B cells, it is the only cell type that exhibits antigenic specificities; achieved by gene rearrangement. T cells are unique with respect to diversity of their subsets, which have distinct effector specificities, proliferative abilities, memory generation, and life span. T cells are impactful in viral infections by virtue of their capability to combat intracellular pathogens. The effector functions of T cells are mediated through cytokines/chemokines and by direct cytotoxicity of infected cells. T cell response can be beneficial or detrimental to host; prognosis depending on qualitative and quantitative differences in the response. Persistent viral infections are associated with functionally suboptimal, exhausted T cell responses, which are unable to clear virus. Specific subsets such as regulatory T cells (Tregs) dampen antiviral responses; thereby favouring viral persistence. However, Tregs protect the host from immunopathology by limiting perpetual inflammation. Certain other subsets such as Th17 cells may contribute to autoimmune component of viral infections. The importance of T cells is highlighted by the fact that modern vaccination and therapeutic approaches focus on modulating T cell frequencies and effector functions. This chapter emphasises the understanding how T cells influence outcomes of viral infections, modern vaccination and therapeutic strategies with thrust on T cell biology. Achanta Jagadeesh, A. M. V. N. Prathyusha, G. Mohana Sheela and Pallaval Veera Bramhachari contributed equally with all other contributors. 140 KeywordsAdaptive immune system · T cell responses · Viral infections · Therapeutic strategies 9.1

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Increased Frequency of Tim-3 Expressing T Cells Is Associated with Symptomatic West Nile Virus Infection

Cited by 17 publications

References 32 publications

Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection

Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection

Blood group A and D negativity are associated with symptomatic West Nile virus infection

T Cells in Viral Infections: The Myriad Flavours of Antiviral Immunity

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