气候变化领域集成服务门户(CCPortal): Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging

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DOI	10.1073/PNAS.2015368117
	Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging
	Inomata M.; Xu S.; Chandra P.; Meydani S.N.; Takemura G.; Philips J.A.; Leong J.M.
发表日期	2021
ISSN	00278424
起始页码	33561
结束页码	33569
卷号	117 期号:52
英文摘要	Streptococcus pneumoniae is a leading cause of pneumonia and invasive disease, particularly, in the elderly. S. pneumoniae lung infection of aged mice is associated with high bacterial burdens and detrimental inflammatory responses. Macrophages can clear microorganisms and modulate inflammation through two distinct lysosomal trafficking pathways that involve 1A/1B-light chain 3 (LC3)-marked organelles, canonical autophagy, and LC3-associated phagocytosis (LAP). The S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers an autophagic response in nonphagocytic cells, but the role of LAP in macrophage defense against S. pneumoniae or in age-related susceptibility to infection is unexplored. We found that infection of murine bone-marrow-derived macrophages (BMDMs) by PLY-producing S. pneumoniae triggered Atg5- and Atg7-dependent recruitment of LC3 to S. pneumoniae-containing vesicles. The association of LC3 with S. pneumoniae-containing phagosomes required components specific for LAP, such as Rubicon and the NADPH oxidase, but not factors, such as Ulk1, FIP200, or Atg14, required specifically for canonical autophagy. In addition, S. pneumoniae was sequestered within single-membrane compartments indicative of LAP. Importantly, compared to BMDMs from young (2-mo-old) mice, BMDMs from aged (20- to 22-mo-old) mice infected with S. pneumoniae were not only deficient in LAP and bacterial killing, but also produced higher levels of proinflammatory cytokines. Inhibition of LAP enhanced S. pneumoniae survival and cytokine responses in BMDMs from young but not aged mice. Thus, LAP is an important innate immune defense employed by BMDMs to control S. pneumoniae infection and concomitant inflammation, one that diminishes with age and may contribute to age-related susceptibility to this important pathogen. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Aging; Autophagy; Bone-marrow-derived macrophages; LC3-associated phagocytosis; Streptococcus pneumoniae
语种	英语
scopus关键词	bacterial protein; lipid; Map1lc3b protein, mouse; microtubule associated protein; plY protein, Streptococcus pneumoniae; reactive oxygen metabolite; streptolysin; aging; animal; autophagy; C57BL mouse; chemistry; host pathogen interaction; immunology; macrophage; male; metabolism; microbial viability; microbiology; mouse; phagocytosis; RAW 264.7 cell line; Streptococcus pneumoniae; ultrastructure; Aging; Animals; Autophagy; Bacterial Proteins; Host-Pathogen Interactions; Lipids; Macrophages; Male; Mice; Mice, Inbred C57BL; Microbial Viability; Microtubule-Associated Proteins; Phagocytosis; RAW 264.7 Cells; Reactive Oxygen Species; Streptococcus pneumoniae; Streptolysins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179686
作者单位	Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, United States; Department of Oral Microbiology, Asahi University School of Dentistry, Mizuho, Gifu, 501-0296, Japan; Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, United States; Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, United States; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, United States; Department of Internal Medicine, Asahi University School of Dentistry, Mizuho, Gifu, 501-0296, Japan
推荐引用方式 GB/T 7714	Inomata M.,Xu S.,Chandra P.,et al. Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging[J],2021,117(52).
APA	Inomata M..,Xu S..,Chandra P..,Meydani S.N..,Takemura G..,...&Leong J.M..(2021).Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Inomata M.,et al."Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).