Interleukin-27 promotes autophagy in human serum-induced primary macrophages via an mTOR- and LC3-independent pathway

Autor: Sylvain Laverdure, Ziqiu Wang, Jun Yang, Takuya Yamamoto, Tima Thomas, Toyotaka Sato, Kunio Nagashima, Tomozumi Imamichi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-021-94061-3
Popis: Abstract Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner.
Databáze: Directory of Open Access Journals
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