Transcriptomic immune profiles of human flavivirus‐specific T‐cell responses

Grifoni, Alba; Tian, Yuan; Sette, Alessandro; Weiskopf, Daniela

doi:10.1111/imm.13161

Cited by 17 publications

(11 citation statements)

References 79 publications

(111 reference statements)

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“…EGR1 is known to regulate IL-2 and TNFα production ( 96 – 98 ). In flavivirus infection, EGR1 was found to be commonly upregulated in T EM and T EMRA in both DENV and Zika virus infection ( 99 ). Furthermore, upon in vitro activation of T cells with DENV peptides, both activated CD4+ ( 100 ) and CD8+ T cells ( 101 ) upregulated EGR1 expression.…”

Section: Discussionmentioning

confidence: 99%

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

et al. 2021

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BackgroundDengue virus (DENV) infection has a global impact on public health. The clinical outcomes (of DENV) can vary from a flu-like illness called dengue fever (DF), to a more severe form, known as dengue hemorrhagic fever (DHF). The underlying innate immune mechanisms leading to protective or detrimental outcomes have not been fully elucidated. Helper innate lymphoid cells (hILCs), an innate lymphocyte recently discovered, functionally resemble T-helper cells and are important in inflammation and homeostasis. However, the role of hILCs in DENV infection had been unexplored.MethodsWe performed flow cytometry to investigate the frequency and phenotype of hILCs in peripheral blood mononuclear cells from DENV-infected patients of different disease severities (DF and DHF), and at different phases (febrile and convalescence) of infection. Intracellular cytokine staining of hILCs from DF and DHF were also evaluated by flow cytometry after ex vivo stimulation. Further, the hILCs were sorted and subjected to transcriptome analysis using RNA sequencing. Differential gene expression analysis was performed to compare the febrile and convalescent phase samples in DF and DHF. Selected differentially expressed genes were then validated by quantitative PCR.ResultsPhenotypic analysis showed marked activation of all three hILC subsets during the febrile phase as shown by higher CD69 expression when compared to paired convalescent samples, although the frequency of hILCs remained unchanged. Upon ex vivo stimulation, hILCs from febrile phase DHF produced significantly higher IFN-γ and IL-4 when compared to those of DF. Transcriptomic analysis showed unique hILCs gene expression in DF and DHF, suggesting that divergent functions of hILCs may be associated with different disease severities. Differential gene expression analysis indicated that hILCs function both in cytokine secretion and cytotoxicity during the febrile phase of DENV infection.ConclusionsHelper ILCs are activated in the febrile phase of DENV infection and display unique transcriptomic changes as well as cytokine production that correlate with severity. Targeting hILCs during early innate response to DENV might help shape subsequent immune responses and potentially lessen the disease severity in the future.

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Section: Discussionmentioning

confidence: 99%

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

et al. 2021

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“…Megapools have also played a key role in extracting and isolating antigen specific T cells for a variety of different indications, and establishing specific immune signatures [153][154][155][156][157][158][159][160][161][162]. The purpose of these studies is to identify specific correlates of immune protection versus immunopathology.…”

Section: Examples Of Practical Application Of Epitope Identification Studiesmentioning

confidence: 99%

Epitope prediction and identification- adaptive T cell responses in humans

Sidney

Peters

Sette

2020

Seminars in Immunology

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“…ZIKV CD4 and CD8 megapool peptides (MP) have been designed and validated, as previously reported ( 34 , 35 ). Briefly, a consensus sequence was generated by MAFFT alignment after querying the availability of NCBI polyprotein ZIKV sequences and BLAST to a corresponding ZIKV isolate being able to represent most of the viral sequence analyzed (ID: 64320) ( 36 ).…”

Section: Methodsmentioning

confidence: 99%

Differential Longevity of Memory CD4 and CD8 T Cells in a Cohort of the Mothers With a History of ZIKV Infection and Their Children

et al. 2021

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Background: Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016–2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones.Results: Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP.Conclusion: Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides.

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Transcriptomic immune profiles of human flavivirus‐specific T‐cell responses

Cited by 17 publications

References 79 publications

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

Epitope prediction and identification- adaptive T cell responses in humans

Differential Longevity of Memory CD4 and CD8 T Cells in a Cohort of the Mothers With a History of ZIKV Infection and Their Children

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