5 research outputs found
Choline acetyltransferase-expressing T cells are required to control chronic viral infection.
peer reviewedAlthough widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity
Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients
We present compelling
evidence for the existence of an extended
innate viperin-dependent pathway, which provides crucial evidence
for an adaptive response to viral agents, such as SARS-CoV-2. We show
the in vivo biosynthesis of a family of novel endogenous cytosine
metabolites with potential antiviral activities. Two-dimensional nuclear
magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system
motif, indicating the presence of an extended panel of urinary metabolites
during the acute viral replication phase. Mass spectrometry additionally
enabled the characterization and quantification of the most abundant
serum metabolites, showing the potential diagnostic value of the compounds
for viral infections. In total, we unveiled ten nucleoside (cytosine-
and uracil-based) analogue structures, eight of which were previously
unknown in humans allowing us to propose a new extended viperin
pathway for the innate production of antiviral compounds.
The molecular structures of the nucleoside analogues and their correlation
with an array of serum cytokines, including IFN-α2, IFN-γ,
and IL-10, suggest an association with the viperin enzyme contributing
to an ancient endogenous innate immune defense mechanism against viral
infection