NAD+ modulation by nicotinamide riboside enhances CD8+ T-cell metabolic fitness and effector function during Trypanosoma cruzi infection and improves parasite control
- 1Universidad Nacional de Cordoba Facultad de Ciencias Quimicas
Abstract
Chagas disease, caused by the parasite Trypanosoma cruzi, remains a major health concern, with effective immune control relying heavily on CD8+ T cells. However, the metabolic factors that regulate CD8+ T cell function during infection are not well understood. Acute T. cruzi infection induced metabolic remodeling in parasite-specific and effector CD8+ T cells, characterized by increased reliance on glycolysis, altered mitochondrial homeostasis, oxidative stress, and increased CD38 expression. Nicotinamide riboside (NR), an NAD+ precursor, improved mitochondrial function, reduced mitochondrial reactive oxygen species (mROS) and CD38 expression, decreased apoptosis, and enhanced CD8+ T cell effector responses in vitro and in infected mice. In vivo, NR treatment increased intracellular NAD+ levels in CD8+ T cells and improved parasite control during acute infection, reducing parasitemia and skeletal muscle parasite burden. Furthermore, transient NR supplementation was associated with persistent metabolic and functional changes in memory CD8+ T cells during chronic infection. These findings identify NAD+ metabolism as a modulator of CD8+ T cell metabolic fitness during T. cruzi infection and support its further investigation as a host-directed strategy to enhance parasite control.
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BibTeX
@misc{hellriegel2026modulation,
title = {{NAD+ modulation by nicotinamide riboside enhances CD8+ T-cell metabolic fitness and effector function during Trypanosoma cruzi infection and improves parasite control}},
author = {F. Hellriegel and C. Fontanari and R. E. Baigorri and M. G. Theumer and C. M. S. Gimenez and M. Herrera and L. Mezzano and C. C. Motran and F. M. Cerban and E. Acosta Rodriguez and L. Berod and C. C. Stempin},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755262},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755262v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - NAD+ modulation by nicotinamide riboside enhances CD8+ T-cell metabolic fitness and effector function during Trypanosoma cruzi infection and improves parasite control
AU - F. Hellriegel
AU - C. Fontanari
AU - R. E. Baigorri
AU - M. G. Theumer
AU - C. M. S. Gimenez
AU - M. Herrera
AU - L. Mezzano
AU - C. C. Motran
AU - F. M. Cerban
AU - E. Acosta Rodriguez
AU - L. Berod
AU - C. C. Stempin
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755262
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755262v1
AB - Chagas disease, caused by the parasite Trypanosoma cruzi, remains a major health concern, with effective immune control relying heavily on CD8+ T cells. However, the metabolic factors that regulate CD8+ T cell function during infection are not well understood. Acute T. cruzi infection induced metabolic remodeling in parasite-specific and effector CD8+ T cells, characterized by increased reliance on glycolysis, altered mitochondrial homeostasis, oxidative stress, and increased CD38 expression. Nicotinamide riboside (NR), an NAD+ precursor, improved mitochondrial function, reduced mitochondrial reactive oxygen species (mROS) and CD38 expression, decreased apoptosis, and enhanced CD8+ T cell effector responses in vitro and in infected mice. In vivo, NR treatment increased intracellular NAD+ levels in CD8+ T cells and improved parasite control during acute infection, reducing parasitemia and skeletal muscle parasite burden. Furthermore, transient NR supplementation was associated with persistent metabolic and functional changes in memory CD8+ T cells during chronic infection. These findings identify NAD+ metabolism as a modulator of CD8+ T cell metabolic fitness during T. cruzi infection and support its further investigation as a host-directed strategy to enhance parasite control.
ER -