Review: the Role and Mechanisms of Macrophage Autophagy in Sepsis

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2018 Sep 9

PMID 30194660

Citations 93

Authors

Peng Qiu

Yang Liu

Jin Zhang

Affiliations

Soon will be listed here.

Abstract

Sepsis is a systemic inflammatory response syndrome caused by infection. The core mechanism underlying sepsis is immune dysfunction, with macrophages, as important cells of the innate immune system, playing an essential role. Autophagy has been shown to be closely related to inflammation and immunity, and autophagy enhancement in sepsis can play a protective role by negatively regulating abnormal macrophage activation, modulating macrophage polarization phenotype, reducing activation of the inflammasome and release of inflammatory factors, and affecting macrophage apoptosis. However, excessive autophagy may also lead to autophagic death of macrophages, which further aggravates the inflammatory response. The mechanisms underlying these functions are relatively complex and remain unclear, but may be related to a variety of signaling pathways such as NF-κB, mTOR, and PI3K/AKT. The administration of drugs to assist in the regulation of macrophage autophagy has become a novel treatment for sepsis. The present review focuses on the role and the potential mechanisms of macrophage autophagy in sepsis.

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References

Pattingre S, Tassa A, Qu X, Garuti R, Liang X, Mizushima N . Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005; 122(6):927-39. DOI: 10.1016/j.cell.2005.07.002. View

Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L . Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol. 2006; 8(10):1124-32. DOI: 10.1038/ncb1482. View

Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan R . Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell. 2007; 128(5):931-46. DOI: 10.1016/j.cell.2006.12.044. View

Colell A, Ricci J, Tait S, Milasta S, Maurer U, Bouchier-Hayes L . GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell. 2007; 129(5):983-97. DOI: 10.1016/j.cell.2007.03.045. View

Xu Y, Jagannath C, Liu X, Sharafkhaneh A, Kolodziejska K, Eissa N . Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity. 2007; 27(1):135-44. PMC: 2680670. DOI: 10.1016/j.immuni.2007.05.022. View

Xu Y, Liu X, Gong X, Eissa N . Signaling pathway of autophagy associated with innate immunity. Autophagy. 2007; 4(1):110-2. DOI: 10.4161/auto.5225. View

Yang C, Kaushal V, Shah S, Kaushal G . Autophagy is associated with apoptosis in cisplatin injury to renal tubular epithelial cells. Am J Physiol Renal Physiol. 2008; 294(4):F777-87. DOI: 10.1152/ajprenal.00590.2007. View

Wang T, Deng J . Molecular and cellular aspects of sepsis-induced immunosuppression. J Mol Med (Berl). 2008; 86(5):495-506. DOI: 10.1007/s00109-007-0300-4. View

Kaushal G, Kaushal V, Herzog C, Yang C . Autophagy delays apoptosis in renal tubular epithelial cells in cisplatin cytotoxicity. Autophagy. 2008; 4(5):710-2. DOI: 10.4161/auto.6309. View

10.

Periyasamy-Thandavan S, Jiang M, Wei Q, Smith R, Yin X, Dong Z . Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. Kidney Int. 2008; 74(5):631-40. DOI: 10.1038/ki.2008.214. View

11.

Saitoh T, Fujita N, Jang M, Uematsu S, Yang B, Satoh T . Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008; 456(7219):264-8. DOI: 10.1038/nature07383. View

12.

Cadwell K, Liu J, Brown S, Miyoshi H, Loh J, Lennerz J . A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008; 456(7219):259-63. PMC: 2695978. DOI: 10.1038/nature07416. View

13.

Lorne E, Zhao X, Zmijewski J, Liu G, Park Y, Tsuruta Y . Participation of mammalian target of rapamycin complex 1 in Toll-like receptor 2- and 4-induced neutrophil activation and acute lung injury. Am J Respir Cell Mol Biol. 2009; 41(2):237-45. PMC: 2715911. DOI: 10.1165/rcmb.2008-0290OC. View

14.

Virgin H, Levine B . Autophagy genes in immunity. Nat Immunol. 2009; 10(5):461-70. PMC: 2715365. DOI: 10.1038/ni.1726. View

15.

Hotchkiss R, Coopersmith C, McDunn J, Ferguson T . The sepsis seesaw: tilting toward immunosuppression. Nat Med. 2009; 15(5):496-7. PMC: 3786779. DOI: 10.1038/nm0509-496. View

16.

Moscat J, Diaz-Meco M . p62 at the crossroads of autophagy, apoptosis, and cancer. Cell. 2009; 137(6):1001-4. PMC: 3971861. DOI: 10.1016/j.cell.2009.05.023. View

17.

Colosetti P, Puissant A, Robert G, Luciano F, Jacquel A, Gounon P . Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy. 2009; 5(8):1092-8. DOI: 10.4161/auto.5.8.9889. View

18.

Droin N, Jacquel A, Hendra J, Racoeur C, Truntzer C, Pecqueur D . Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation of monocytes in chronic myelomonocytic leukemia. Blood. 2009; 115(1):78-88. DOI: 10.1182/blood-2009-05-224352. View

19.

Mortensen M, Ferguson D, Edelmann M, Kessler B, Morten K, Komatsu M . Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci U S A. 2010; 107(2):832-7. PMC: 2818953. DOI: 10.1073/pnas.0913170107. View

20.

Geissmann F, Manz M, Jung S, Sieweke M, Merad M, Ley K . Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327(5966):656-61. PMC: 2887389. DOI: 10.1126/science.1178331. View