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Papers of the Week


Papers: 16 Dec 2023 - 22 Dec 2023


2023 Dec 15


iScience


38125023


26


12

Leishmania mexicana promotes pain-reducing metabolomic reprogramming in cutaneous lesions.

Authors

Volpedo G, Oljuskin T, Cox B, Mercado Y, Askwith C, Azodi N, Bernier M, Nakhasi HL, Gannavaram S, Satoskar AR

Abstract

Cutaneous leishmaniasis (CL) is characterized by extensive skin lesions, which are usually painless despite being associated with extensive inflammation. The molecular mechanisms responsible for this analgesia have not been identified. Through untargeted metabolomics, we found enriched anti-nociceptive metabolic pathways in -infected mice. Purines were elevated in infected macrophages and at the lesion site during chronic infection. These purines have anti-inflammatory and analgesic properties by acting through adenosine receptors, inhibiting TRPV1 channels, and promoting IL-10 production. We also found arachidonic acid (AA) metabolism enriched in the ear lesions compared to the non-infected controls. AA is a metabolite of anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These endocannabinoids act on cannabinoid receptors 1 and 2 and TRPV1 channels to exert anti-inflammatory and analgesic effects. Our study provides evidence of metabolic pathways upregulated during infection that may mediate anti-nociceptive effects experienced by CL patients and identifies macrophages as a source of these metabolites.