Exosomal programmed death ligand 1 in patients with Mycobacterium avium complex lung disease

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ID: 323175
2026
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Abstract
BACKGROUND: Mycobacterium avium complex lung disease (MAC-LD) is increasing worldwide. Exosomal programmed death-ligand 1 (PD-L1) has been scarcely investigated in MAC-LD. METHODS: Plasma exosomes and their PD-L1 from MAC-LD patients and healthy controls were measured and used for co-culturing Jurkat cells with or without PD-L1/PD-1 blocking antibodies. MAC-infected mice were treated with exosome inhibitors to assess exosomal PD-L1 and bacterial burden. RESULTS: Plasma exosomal PD-L1 levels were significantly higher in MAC-LD patients (1,477±1,243 pg/mL) vs. controls (183.8±113.9 pg/mL; P < .001), correlated with cavitary disease (2,415±1,309 vs. 844.1±652.2 pg/mL; P = .008) and decreased after treatment (1,474±961.3 vs. 738.5±820.4 pg/mL; P = .03). MAC-infected macrophage exosomes decreased Jurkat cell survival (72.9±11.5% vs. 98.2±0.6%; P < .01), which could be reversed by PD-L1/PD-1 antibodies. In the mouse study, GW4869 (an exosome biogenesis inhibitor) reduced lung exosomal PD-L1 (497.6±123.1 to 197.7±116.4 pg/mL; P = .008) and bacterial load (996,400±96,316 to 116,400±18,528 CFU; P = .008), whereas DMA (an exosome release inhibitor) showed no significant effect on lung exosome and bacterial load. CONCLUSIONS: Exosomal PD-L1 promotes immune suppression and reflects disease severity in MAC-LD. Inhibition of exosome biogenesis reduced exosomal PD-L1 levels and MAC burden in lung, supporting a potential therapeutic avenue that requires further validation.
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Authors Chi-Yu Hsu, Bo‐Shiun Yan, Juo-Hsin Lai, Yu‐Li Lin, Chun-Kai Pan, Tsung-Hsuan Huang, Jyy-Jih Tsai-Wu, Yin-Wen Shiue, Chin‐Chung Shu
Journal The Journal of infectious diseases
Year 2026
DOI
10.1093/infdis/jiag391
URL
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