title: Autophagy regulates phagocytosis by modulating the expression of scavenger receptors.
abstract: Autophagy and phagocytosis are conserved cellular functions involved in innate immunity. However, the nature of their interactions remains unclear. We evaluated the role of autophagy in regulating phagocytosis in macrophages from myeloid-specific autophagy-related gene 7-deficient (Atg7⁻/⁻) mice. Atg7⁻/⁻ macrophages exhibited higher bacterial uptake when infected with Mycobacterium tuberculosis (Mtb) or with M. tuberculosis var. bovis BCG (BCG). In addition, BCG-infected Atg7⁻/⁻ mice showed increased bacterial loads and exacerbated lung inflammatory responses. Atg7⁻/⁻ macrophages had increased expression of two class A scavenger receptors: macrophage receptor with collagenous structure (MARCO) and macrophage scavenger receptor 1 (MSR1). The increase in scavenger receptors was caused by increased activity of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) transcription factor resulting from accumulated sequestosome 1 (SQSTM1 or p62) in Atg7⁻/⁻ macrophages. These insights increase our understanding of the host-pathogen relationship and suggest that therapeutic strategies should be designed to include modulation of both phagocytosis and autophagy.
authors.affiliation: Department of Medicine Pulmonary and Critical Care Section, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Bonilla
authors.forename: Abhisek
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Youbao
authors.initials: Y
authors.lastname: Sha
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiang
authors.forename: Arshad
authors.initials: A
authors.lastname: Kan
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Jagannath
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: N Tony
authors.initials: NT
authors.lastname: Eissa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000276:immunology*; D000071193:Autophagy-Related Protein 7; D058491:Bacterial Load / Q000276:immunology; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009164:Mycobacterium Infections / Q000276:immunology; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D051116:Receptors, Scavenger / Q000096:biosynthesis / Q000276:immunology; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis*; D000071456:Sequestosome-1 Protein; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502661:Atg7 protein, mouse; D006360:Heat-Shock Proteins; C092228:Marco protein, mouse; D008869:Microtubule-Associated Proteins; C495140:Msr1 protein, mouse; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D000071193:Autophagy-Related Protein 7
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