Inhibition of Mitochondrial Translation Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation by Targeting Vγ4+ γδ T Cells.

Psoriasis is an inflammatory skin disorder that is characterized by keratinocyte hyperproliferation in response to immune cell infiltration and cytokine secretion in the dermis. γδ T cells expressing the Vγ4 TCR chain are among the highest contributors of IL-17A, which is a major cytokine that drives a psoriasis flare, making Vγ4 γδ T cells a suitable target to restrict psoriasis progression. In this study, we demonstrate that mitochondrial translation inhibition within Vγ4 γδ T cells effectively reduced erythema, scaling, and skin thickening in a murine model of psoriatic disease.

Multiplexes Death-Effector Deoxyribonucleosides to Neutralize Phagocytes.

Adenosine synthase A (AdsA) is a key virulence factor of , a dangerous microbe that causes fatal diseases in humans. Together with staphylococcal nuclease, AdsA generates deoxyadenosine (dAdo) from neutrophil extracellular DNA traps thereby igniting caspase-3-dependent cell death in host immune cells that aim at penetrating infectious foci. Powered by a multi-technological approach, we here illustrate that the enzymatic activity of AdsA in abscess-mimicking microenvironments is not restricted to the biogenesis of dAdo but rather comprises excessive biosynthesis of deoxyguanosine (dGuo), a cytotoxic deoxyribonucleoside generated by to eradicate macrophages of human and animal origin.

Methicillin-resistant synthesizes deoxyadenosine to cause persistent infection.

Methicillin-resistant (MRSP) is an emerging zoonotic pathogen of canine origin that causes an array of fatal diseases, including bacteremia and endocarditis. Despite large-scale genome sequencing projects have gained substantial insights into the genomic landscape of MRSP, current knowledge on virulence determinants that contribute to pathogenesis during human or canine infection is very limited. Using a panel of genetically engineered MRSP variants and a mouse abscess model, we here identified the major secreted nuclease of designated NucB and adenosine synthase A (AdsA) as two synergistically acting enzymes required for MRSP pathogenesis.