Table1.

Current evidence of the cross-talk between autophagy and phagocytosis.

-	Phagocyte	Disease/Model	Relationship	Mechanism	Refs.
Autophagy is negatively correlated with phagocytosis	In vitro studies
	Macrophages	Infecting macrophages with Mtb or BCG	Myeloid-specific Atg7-/- macrophages exhibited higher Mtb and BCG uptake	Accumulating SQSTM1 activated Nrf2, leading to upregulation of MSR1 and MARCO	[2]
	Dendritic cells	Irradiating live EG7 cells with γ-ray, and then coculturing with BMDCs	Atg5-deficient dendritic cells showed increased phagocytosis of apoptotic tumor cells	Increased expression of scavenger receptor CD36	[6]
	Macrophages	Macrophages were exposed to CFDA-SE-labeled Escherichia coli K-12, CFDA-SE-labeled Lactobacillus reuteri ATCC PTA 6475, or Fluoresbrite YG microsphere	Decreased phagocytosis was seen in Hrh2-/- macrophages with increased expression of autophagy genes Beclin-1 and ATG12	Increased Beclin-1 and ATG12 expression was accompanied by decreased MSR1 expression and MSR1 surface abundance in Hrh2-/- macrophages	[11]
	Macrophages	Coculturing heat inactivated yeast particles or L. amazonensis stationary phase promastigotes with macrophages	Autophagy induced by physiological (starvation) and pharmacological (rapamycin) methods was shown to reduce the phagocytic capacity of murine macrophages	Inhibiting particle internalization	[126]
	Macrophages	Infecting RAW264.7 cells with ST239-MRSA	Autophagy inhibitor 3-MA promoted phagocytosis of macrophage	-	[127]
	In vivo studies
	Macrophages	Intranasally infecting mice with BCG	Atg7-/- mice showed increased bacterial loads	-	[2]
	Dendritic cells	Injecting apoptotic tumor cells into the footpads of the indicated mice	Atg5-deficient dendritic cells showed increased phagocytosis of apoptotic tumor cells	Increased expression of scavenger receptor CD36	[6]
	Macrophages	Intranasally inserting ST239-MRSA to establish mouse pneumonia model	Autophagy inhibitor 3-MA protected mice from MRSA pneumonia	-	[127]
	Glia	Knocking down Draper (isoform I) in cortex glia in the brain of Drosophila melanogaster	Inactivating autophagy through TORC1 activation could rescue the accumulation of apoptotic neurons in the brain of Draper-/- deficient Drosophila melanogaster	-	[128]
	Microglia	AD patients carrying TREM2 risk variants; TREM2-deficient mice with AD-like pathology	Increased autophagy was detected in TREM2-deficient microglia and in AD patients carrying TREM2 variants	TREM2 maintained microglia at high metabolic states through enhanced activation of the mTOR pathway	[130]
	Neutrophils	NLRP3-deficient (Nlrp3-/-) mice in polymicrobial sepsis model induced by CLP	HMGB1-/- peritoneal cells (primarily neutrophils) showed decreased autophagy and augmented phagocytosis	-	[131]
Autophagy is positively correlated with phagocytosis	In vitro studies
	Microglia	LPS treated microglia was incubated with Aβ1−42 fibrils	TLR4 activation induced by LPS suppressed autophagy and impaired phagocytic capacity of microglia	-	[121]
	Macrophages	Macrophages were exposed to apoptotic lymphocytes or Jurkat T cells induced by cyclophosphamide	Autophagy inhibitor 3-MA decreased phagocytosis of the apoptotic cells by macrophages	-	[138]
-	Phagocyte	Disease/Model	Relationship	Mechanism	Refs.
	Microglia	Uptake of latex beads for Beclin-1 knockdown BV2 microglial cells	Reducing microglial Beclin-1 levels significantly impaired phagocytosis, and phagocytosis was “rescued” by recovering Beclin-1 levels with a lentivirus encoding mouse Beclin-1	Reduced Beclin-1 disrupted retromer-mediated recycling of phagocytic receptors CD36 and TREM2	[139]
	Microglia	Incubation of DJ-1 deficient microglia with α-syn.	DJ-1 deficiency impaired autophagy and reduced uptake and clearance of α-syn in the phagocytosis in microglia	-	[144]
	In vivo studies
	Microglia	Injecting fibrillar Aβ into the frontal cortex of Beclin-1+/- mice	Reduced microglial Beclin-1 impaired Aβ phagocytosis	-	[139]
	Epithelial hyp7 cell	Apoptotic C. elegans apoptotic Q cells degraded by epithelial an hyp7 cell	Autophagy proteins LC3, ATG-18, EPG-5 act within the phagocyte to promote apoptotic cell degradation	ATG18 and EPG-5loss showed delayed recruitment of RAB-5, RAB-7, and lysosomal markers onto the apoptotic Q cell corpse	[143]

Abbreviations: Mtb: Mycobacterium tuberculosis; BCG: M. tuberculosis var. bovisBCG;MSR1: Macrophage scavenger receptor 1; MARCO: macrophage receptor with collagenous structure; BMDCs: Bone marrow-derived dendritic cells; Hrh2: histamine H2 receptor gene; MRSA: Methicillin-resistant Staphylococcus aureus; TORC1: Target of Rapamycin Complex 1; TREM2: Triggering receptor expressed on myeloid cells 2; mTOR: mammalian target of rapamycin; CLP: cecal ligation and puncture; LPS:lipopolysaccharide; Aβ:β-amyloid; TLR4: Toll-like receptor 4;α-syn: α -synuclein.