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

Noor Zayanah Hamis; Justin S.G. Ooi; Ka Wai Cheung; Valerie Chew; Michaela Gregorova; Eugenia Ziying Ong; Kuan Rong Chan; Tun Linn Thein; 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 S.G. Ooi
, Ka Wai Cheung
, Valerie Chew
, Michaela Gregorova
, Eugenia Ziying Ong
, Kuan Rong Chan
, Tun Linn Thein
, David Chien Boon Lye
, Eng Eong Ooi
, Laura Rivino

University of Bristol
Duke-NUS Medical School
National Centre for Infectious Diseases
Tan Tock Seng Hospital
National University of Singapore
Lee Kong Chian School of Medicine
Communicable Diseases Agency
SingHealth Duke-NUS Academic Medical Centre

Research output: Contribution to journal › Article › 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 (T_RM) cells, supporting their differentiation to the T_RM 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 T_RM cells to enhance protective immunity.

Original language	English
Article number	eaea7987
Journal	Science advances
Volume	12
Issue number	12
DOIs	https://doi.org/10.1126/sciadv.aea7987
Publication status	Published - 20 Mar 2026
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

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10.1126/sciadv.aea7987Licence: CC BY

Cite this

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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.",

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

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doi = "10.1126/sciadv.aea7987",

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T1 - Dengue infection elicits skin tissue-resident and circulating CD8+ T cells associated with protection from hospitalization

AU - Hamis, Noor Zayanah

AU - Ooi, Justin S.G.

AU - Cheung, Ka Wai

AU - Chew, Valerie

AU - Gregorova, Michaela

AU - Ong, Eugenia Ziying

AU - Chan, Kuan Rong

AU - Thein, Tun Linn

AU - Lye, David Chien Boon

AU - Ooi, Eng Eong

AU - Rivino, Laura

PY - 2026/3/20

Y1 - 2026/3/20

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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