Dengue infection elicits skin tissue-resident and circulating CD8+ T cells associated with protection from hospitalization

Noor Zayanah Hamis; Justin Sg Ooi; Ka-Wai Cheung; Valerie Chew; Michaela Gregorova; Eugenia Ziying Ong; Kuan Rong Chan; Tun-Linn Thein; Yee-Sin Leo; David Chien Boon Lye; Eng Eong Ooi; Laura Rivino

doi:10.1126/sciadv.aea7987

Dengue infection elicits skin tissue-resident and circulating CD8+ T cells associated with protection from hospitalization

Noor Zayanah Hamis, Justin Sg Ooi, Ka-Wai Cheung, Valerie Chew, Michaela Gregorova, Eugenia Ziying Ong, Kuan Rong Chan, Tun-Linn Thein, Yee-Sin Leo, David Chien Boon Lye, Eng Eong Ooi, Laura Rivino^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Dengue is spreading globally, and there is urgent need to define immune correlates of protection for this disease. Dengue infection first occurs in the skin following the bite of an infected mosquito; however, knowledge of host immune responses within this site remains sparse. We investigated the phenotypic, functional, and transcriptional profiles of skin and blood T cells in 73 patients with dengue and 10 healthy volunteers. We show that the skin T cell compartment undergoes marked reshaping and is strongly enriched with proliferating CD4+ and CD8+ T cells compared with the blood of patients. Activated skin CD8+ T cells expressed a core transcriptional signature of tissue-resident memory T (TRM) cells, supporting their differentiation to the TRM cell lineage during infection. The magnitude of skin and blood CD8+ T cell responses were associated with protection from hospitalization in this cohort. These data support a protective role of skin-resident and circulating CD8+ T cells in dengue and warrant evaluation of vaccination strategies inducing skin TRM cells to enhance protective immunity.

Original language	English
Article number	eaea7987
Number of pages	15
Journal	Science Advances
Volume	12
Issue number	12
DOIs	https://doi.org/10.1126/sciadv.aea7987
Publication status	Published - 20 Mar 2026

Bibliographical note

Publisher Copyright:
© 2026 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Humans
CD8-Positive T-Lymphocytes/immunology
Dengue/immunology
Skin/immunology
Hospitalization
Female
Adult
Male
Immunologic Memory
CD4-Positive T-Lymphocytes/immunology
Middle Aged
Dengue Virus/immunology
Memory T Cells/immunology

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Hamis, N. Z., Ooi, J. S., Cheung, K.-W., Chew, V., Gregorova, M., Ong, E. Z., Chan, K. R., Thein, T.-L., Leo, Y.-S., Lye, D. C. B., Ooi, E. E., & Rivino, L. (2026). Dengue infection elicits skin tissue-resident and circulating CD8+ T cells associated with protection from hospitalization. Science Advances, 12(12), Article eaea7987. https://doi.org/10.1126/sciadv.aea7987

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title = "Dengue infection elicits skin tissue-resident and circulating CD8+ T cells associated with protection from hospitalization",

abstract = "Dengue is spreading globally, and there is urgent need to define immune correlates of protection for this disease. Dengue infection first occurs in the skin following the bite of an infected mosquito; however, knowledge of host immune responses within this site remains sparse. We investigated the phenotypic, functional, and transcriptional profiles of skin and blood T cells in 73 patients with dengue and 10 healthy volunteers. We show that the skin T cell compartment undergoes marked reshaping and is strongly enriched with proliferating CD4+ and CD8+ T cells compared with the blood of patients. Activated skin CD8+ T cells expressed a core transcriptional signature of tissue-resident memory T (TRM) cells, supporting their differentiation to the TRM cell lineage during infection. The magnitude of skin and blood CD8+ T cell responses were associated with protection from hospitalization in this cohort. These data support a protective role of skin-resident and circulating CD8+ T cells in dengue and warrant evaluation of vaccination strategies inducing skin TRM cells to enhance protective immunity.",

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author = "Hamis, \{Noor Zayanah\} and Ooi, \{Justin Sg\} and Ka-Wai Cheung and Valerie Chew and Michaela Gregorova and Ong, \{Eugenia Ziying\} and Chan, \{Kuan Rong\} and Tun-Linn Thein and Yee-Sin Leo and Lye, \{David Chien Boon\} and Ooi, \{Eng Eong\} and Laura Rivino",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.",

year = "2026",

month = mar,

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doi = "10.1126/sciadv.aea7987",

language = "English",

volume = "12",

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AU - Hamis, Noor Zayanah

AU - Ooi, Justin Sg

AU - Cheung, Ka-Wai

AU - Chew, Valerie

AU - Gregorova, Michaela

AU - Ong, Eugenia Ziying

AU - Chan, Kuan Rong

AU - Thein, Tun-Linn

AU - Leo, Yee-Sin

AU - Lye, David Chien Boon

AU - Ooi, Eng Eong

AU - Rivino, Laura

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N2 - Dengue is spreading globally, and there is urgent need to define immune correlates of protection for this disease. Dengue infection first occurs in the skin following the bite of an infected mosquito; however, knowledge of host immune responses within this site remains sparse. We investigated the phenotypic, functional, and transcriptional profiles of skin and blood T cells in 73 patients with dengue and 10 healthy volunteers. We show that the skin T cell compartment undergoes marked reshaping and is strongly enriched with proliferating CD4+ and CD8+ T cells compared with the blood of patients. Activated skin CD8+ T cells expressed a core transcriptional signature of tissue-resident memory T (TRM) cells, supporting their differentiation to the TRM cell lineage during infection. The magnitude of skin and blood CD8+ T cell responses were associated with protection from hospitalization in this cohort. These data support a protective role of skin-resident and circulating CD8+ T cells in dengue and warrant evaluation of vaccination strategies inducing skin TRM cells to enhance protective immunity.

AB - Dengue is spreading globally, and there is urgent need to define immune correlates of protection for this disease. Dengue infection first occurs in the skin following the bite of an infected mosquito; however, knowledge of host immune responses within this site remains sparse. We investigated the phenotypic, functional, and transcriptional profiles of skin and blood T cells in 73 patients with dengue and 10 healthy volunteers. We show that the skin T cell compartment undergoes marked reshaping and is strongly enriched with proliferating CD4+ and CD8+ T cells compared with the blood of patients. Activated skin CD8+ T cells expressed a core transcriptional signature of tissue-resident memory T (TRM) cells, supporting their differentiation to the TRM cell lineage during infection. The magnitude of skin and blood CD8+ T cell responses were associated with protection from hospitalization in this cohort. These data support a protective role of skin-resident and circulating CD8+ T cells in dengue and warrant evaluation of vaccination strategies inducing skin TRM cells to enhance protective immunity.

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KW - CD8-Positive T-Lymphocytes/immunology

KW - Dengue/immunology

KW - Skin/immunology

KW - Hospitalization

KW - Female

KW - Adult

KW - Male

KW - Immunologic Memory

KW - CD4-Positive T-Lymphocytes/immunology

KW - Middle Aged

KW - Dengue Virus/immunology

KW - Memory T Cells/immunology

U2 - 10.1126/sciadv.aea7987

DO - 10.1126/sciadv.aea7987

M3 - Article (Academic Journal)

C2 - 41861003

SN - 2375-2548

VL - 12

JO - Science Advances

JF - Science Advances

IS - 12

M1 - eaea7987

ER -

Dengue infection elicits skin tissue-resident and circulating CD8+ T cells associated with protection from hospitalization

Abstract

Bibliographical note

UN SDGs

Keywords

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