title: IL-17A and IL-17F induce autophagy in RAW 264.7 macrophages.
abstract: Autophagy is an important cellular catabolic process for the lysosomal degradation of cytoplasmic organelles, proteins and microorganisms. The autophagic process is intertwined with the immune response: autophagy regulates both innate and adaptive immunity, conversely, cytokines produced during the course of the immune response modulate various functions of the autophagic cascade. The IL-17 family member cytokines play a pivotal role in immune protection against extra- and intracellular bacterial pathogens. Since the effects of IL-17A and IL-17F on autophagy have not yet been reported, we have evaluated the autophagic activity in the RAW 264.7 cell line treated with either IL-17A or IL-17F. Both IL-17A and IL-17F proved to promote microtubule-associated protein 1 light chain 3 B-II (LC3B-II) accumulation, enhance the autophagic flux, facilitate the intracellular redistribution of LC3B, increase both the average number and the size of autophagosomes per cell, and foster the formation of acidic vesicular organelles. IL-17F was considerably more efficient than IL-17A in promoting the autophagic process. Further experiments to determine the potential effect of IL-17-induced autophagy on the antibacterial activity of RAW macrophages revealed that IL-17F significantly decreased the intracellular counts of Mycobacterium terrae, while the colony-forming unit values remained comparable in the IL-17A-treated cells and the control cultures. In conclusion, these results demonstrate that IL-17A and IL-17F are capable of inducing autophagy in macrophages, and thereby contribute to the elimination of Mycobacterium terrae. These data may bear on the pathogenesis of infections caused by Mycobacterium terrae, as IL-17 plays a pivotal role in the immune response to mycobacteria. IL-17-mediated activation of autophagy may also be implicated in various infections and other pathological conditions.
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Orosz
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Elena Gouitel
authors.initials: EG
authors.lastname: Papanicolaou
authors.affiliation: Department of Medical Biology, Faculty of Medicine, University of Szeged, Somogyi Béla u. 4, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Seprényi
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary. Electronic address: megyeri.klara@med.u-szeged.hu.
authors.forename: Klára
authors.initials: K
authors.lastname: Megyeri
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009170:Nontuberculous Mycobacteria / Q000378:metabolism*; D000067996:RAW 264.7 Cells
chemical_list: C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; D008869:Microtubule-Associated Proteins
keywords: Autophagy; IL-17A; IL-17F; Macrophage; Mycobacterium terra