TY - JOUR
T1 - Autophagy regulates phagocytosis by modulating the expression of scavenger receptors
AU - Bonilla, Diana L.
AU - Bhattacharya, Abhisek
AU - Sha, Youbao
AU - Xu, Yi
AU - Xiang, Qian
AU - Khan, Arshad
AU - Jagannath, Chinnaswamy
AU - Komatsu, Masaaki
AU - Eissa, N. Tony
N1 - Funding Information:
The authors thank scientists who contributed reagents, as outlined in the text, and members of the N.T.E. laboratory for useful discussions. This study is supported by Heart Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, and the American Heart Association. This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the National Institutes of Health (NIAID P30AI036211, NCI P30CA125123, and NCR S10RR024574) and the assistance of J.M. Sederstrom.
PY - 2013/9/19
Y1 - 2013/9/19
N2 - 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). Inaddition, 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.
AB - 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). Inaddition, 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.
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U2 - 10.1016/j.immuni.2013.08.026
DO - 10.1016/j.immuni.2013.08.026
M3 - Article
C2 - 24035364
AN - SCOPUS:84884340814
SN - 1074-7613
VL - 39
SP - 537
EP - 547
JO - Immunity
JF - Immunity
IS - 3
ER -