Autophagy and phagocytosis are highly conserved cellular functions involved in innate immunity. However, the nature of the interactions between these two critical processes remains essentially unknown. We evaluated the role of autophagy in regulating phagocytosis by measuring phagocytic activity in autophagy-deficient macrophages obtained from a myeloid-specific autophagy-related gene 7 knockout mice Atg7-/-. Importantly, in addition to increased mycobacterial growth, Atg7-/- macrophages exhibited higher bacterial uptake, when infected with Mycobacterium tuberculosis or M. tuberculosis var. bovis BCG. In addition, Atg7-/- mice, infected intranasally with BCG, showed increased bacterial loads and exacerbated inflammatory responses in lungs, compared to Atg7+/+ cells. Atg7-/- macrophages had increased surface expression of two class A scavenger receptors: macrophage receptor with collagenous structure MARCO and scavenger receptor-A. These findings were confirmed in Atg3-/-, Atg5-/- and Atg7-/- mouse embryonic fibroblasts. The increased surface expression of scavenger receptors was caused by increased activity of the transcription factor NF-E2-related factor 2 due to accumulation of p62 in autophagy-deficient macrophages. These new insights increase our understanding of host-pathogen relationship and suggest that therapeutic strategies against pathogens should be designed to include modulation of both phagocytosis and autophagy.
- Copyright © 2013 by The American Association of Immunologists, Inc.