Autophagy regulates phagocytosis by modulating the expression of scavenger receptors

Diana L. Bonilla, Abhisek Bhattacharya, Youbao Sha, Yi Xu, Qian Xiang, Arshad Khan, Chinnaswamy Jagannath, Masaaki Komatsu, N. Tony Eissa

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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). 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.

Original languageEnglish (US)
Pages (from-to)537-547
Number of pages11
JournalImmunity
Volume39
Issue number3
DOIs
StatePublished - Sep 19 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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