IMMUNOLOGY2026™ Conference Recordings For Attendees-The nucleoside transporter SLC29a3 supports phagosomal TLR signaling and TRPML1 activity in dendritic cells

The nucleoside transporter SLC29a3 supports phagosomal TLR signaling and TRPML1 activity in dendritic cells

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Video Summary

Adriana Mantegazza presented work on the lysosomal nucleoside transporter SLC29A3, mutated in H syndrome, and how its loss disrupts dendritic cell function. Her lab showed that SLC29A3 normally exports nucleosides from lysosomes/phagosomes, helping maintain acidic pH. In knockout cells, phagosomes became more alkaline, which impaired antigen degradation, endosomal TLR7 cleavage/signaling, and production of cytokines and chemokines after stimulation with TLR ligands or bacteria. Antigen presentation to OT-II T cells was also reduced, largely due to defective processing and phagosomal tubulation.  <br /><br />She further found that SLC29A3 loss impaired TRPML1-dependent lysosomal calcium signaling, preventing TFEB activation, reducing lysosomal/autophagy gene programs, and weakening an anti-inflammatory pathway. Overall, the study links nucleoside transport, phagosomal acidification, innate sensing, antigen presentation, and autophagy to inflammation in H syndrome.

Meta Tag

Date April 16, 2026 8:00 AM - 9:30 AM

Room 104C

Session New Insights into the Role of Ion Channels and Transporters in Immunity, Sponsored by the Society of General Physiologists

Speaker Adriana Mantegazza

Track Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

Year 2026

Keywords

SLC29A3

lysosomal nucleoside transporter

dendritic cell dysfunction

phagosomal acidification

H syndrome

April 16, 2026 8:00 AM - 9:30 AM

104C

New Insights into the Role of Ion Channels and Transporters in Immunity, Sponsored by the Society of General Physiologists

Adriana Mantegazza

Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

2026