Biology subjects

Rivino, L.

Publications and source records attributed to Rivino, L..

3 recordsLinked to original sources

bioRxiv2025

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

Dengue is spreading globally and there is urgent need to define immune correlates of protection against this disease. Immune responses against dengue viruses have been studied in blood samples of dengue patients. However, dengue virus infection first occurs in the skin following the bite of an infected Aedes mosquito, and immune responses are initiated within this site. In this study, we investigated the phenotypic, functional and transcriptional profiles of skin and blood T-cell responses and their role in immunity in 73 dengue patients and 10 healthy volunteers. We show that the skin T-cell compartment undergoes dramatic reshaping compared to the blood of dengue patients. CD4+ and CD8+ T-cell responses were highly enriched in the skin compared to the blood of the same patients, and skin-based T-cells expressed markers associated with tissue-resident T (TRM) cells. While the magnitude of the CD4+ T-cell response in the skin was independent to that in the blood, CD8+ T-cell responses in skin and blood were positively correlated. Activated CD8+ T-cells in the skin expressed a core transcriptional signature of TRM cells, further supporting their differentiation to the TRM lineage during infection. The magnitude of both skin and blood CD8+ T-cell responses was associated with protection from hospitalization in this cohort. These data collectively support a protective role of skin-resident and circulating CD8+ T-cells in dengue and provide insights into the biology of TRM cells in human infection. Our findings warrant evaluation of vaccination strategies that induce TRM cells in the skin to enhance protection against dengue. One Sentence SummaryDengue infection elicits skin tissue-resident and circulating CD8+ T-cells associated with protection from hospitalization in adult dengue patients.

immunology↗

bioRxiv2024

Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight

Dengue is a mosquito-borne virus infection affecting half of the worlds population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who will progress to severe dengue (SD) from those who do not. In patients with overweight/obesity these signatures are exacerbated compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+ T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic capacity compared to non-SD. Furthermore, type-I Interferon signalling is downregulated in SD, suggesting defective virus-sensing mechanisms may underlie NK/T-cell dysfunction. We propose that dysfunctional "professional killer" T/NK-cells underpin dengue pathogenesis. Our findings pave the way for the evaluation of immunomodulatory therapies for dengue.

immunology↗

bioRxiv2024

Impact of cryopreservation on immune cell metabolism as measured by SCENITH.

The dynamic functioning of immune cells is regulated by cellular metabolic processes, and there is growing interest in the study of immunometabolic correlates of dysfunctional immune responses. SCENITH is a novel flow cytometry-based technique that allows for ex vivo metabolic profiling of immune cells within heterogeneous samples. Cryopreservation of clinical samples is frequently undertaken to facilitate high throughput processing, but is thought to lead to cellular metabolic dysfunction. We aimed to investigate the impact of cryopreservation on immune cell metabolism, harnessing SCENITHs unique ability to describe the divergent bioenergetic characteristics of distinct immune cell subsets. We demonstrate that T cells undergoing activation with a CD3/CD28 stimulus are less readily metabolically reprogrammed following cryopreservation. Additionally, we find that cryopreservation introduces a time-dependent metabolic artefact that favours glycolysis and impairs oxidative phosphorylation, suggesting that cryopreservation results in mitochondrial dysfunction. Despite this artefact, SCENITH was still able to reveal the distinct bioenergetic profiles of contrasting immune cells populations following cryopreservation - for example, non-classical monocytes have a higher mitochondrial dependence than classical monocytes, and T cell CD69 expression is associated with an upregulation of glycolytic capacity. Whilst we believe that SCENITH can provide valuable information about immune cell metabolism even in cryopreserved samples, our findings have important implications for the design of future studies. Investigators should carefully consider how to process and store clinical samples to ensure that cryopreservation does not confound analyses, particularly where longitudinal sampling is required.

immunology↗