SNX10 promotes phagosome maturation in macrophages and protects mice against<i>Listeria monocytogenes</i>infection

Lou, Jun; Li, Xiawei; Huang, Wei; Liang, Jingjing; Zheng, Mingzhu; Xu, Ting; Lyu, Jun; Li, Dan; Xu, Qin; Jin, Xuexiao; Fu, Guotong; Wang, Di; Lu, Linrong

doi:10.18632/oncotarget.19644

Cited by 23 publications

(27 citation statements)

References 39 publications

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“…Accordingly, SNX1 organizes a tubular network during establishment of the Salmonella -containing vacuole (SCV; Bujny et al, 2008 ), while depletion of SNX3 leads to reduced formation of Salmonella -induced filaments ( Braun et al, 2010 ). Recently, Chlamydia trachomatis was shown to hijack SNX5, resulting in disrupted retromer trafficking ( Elwell et al, 2017 ; Paul et al, 2017 ), whereas SNX10 was found to promote phagosome maturation and protect against infection with Listeria monocytogenes ( Lou et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

SNX3 drives maturation of Borrelia phagosomes by forming a hub for PI(3)P, Rab5a, and galectin-9

Klose

Salloum

Gonschior

et al. 2019

Journal of Cell Biology

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The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, is internalized by macrophages and processed in phagolysosomes. Phagosomal compaction, a crucial step in phagolysosome maturation, is driven by contact of Rab5a-positive vesicles with the phagosomal coat. We show that the sorting nexin SNX3 is transported with Rab5a vesicles and that its PX domain enables vesicle–phagosome contact by binding to PI(3)P in the phagosomal coat. Moreover, the C-terminal region of SNX3 recruits galectin-9, a lectin implicated in protein and membrane recycling, which we identify as a further regulator of phagosome compaction. SNX3 thus forms a hub for two distinct vesicle populations, constituting a convergence point for the endosomal recycling machinery, to contribute to phagosome maturation and intracellular processing of borreliae. These data also suggest that the helical shape of B. burgdorferi itself, providing sites of high curvature and thus local PI(3)P enrichment at phagosomes, may be one of the driving elements underlying the efficient elimination of spirochetes by immune cells.

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Section: Introductionmentioning

confidence: 99%

SNX3 drives maturation of Borrelia phagosomes by forming a hub for PI(3)P, Rab5a, and galectin-9

Klose

Salloum

Gonschior

et al. 2019

Journal of Cell Biology

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“…SNX10 has been found to play an important role in embryonic development [ 11 ] , alcohol-induced liver injury and steatosis [ 13 ] , osteoclast formation and resorption activity [ 14 , 15 ] , colorectal cancer [ 16 ] , and phagosome maturation in macrophages [ 17 ] . However, little is known about its role in cardiac disease.…”

Section: Discussionmentioning

confidence: 99%

Does Decreased SNX10 Serve as a Novel Risk Factor in Atrial Fibrillation of the Valvular Heart Disease? – A Case-Control Study

Yao¹,

Hou²,

Lv³

et al. 2021

Braz J Cardiovasc Surg

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Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia. Sorting nexin 10 (SNX10) has been reported to be an important regulator in embryonic development and human diseases, however, little is known about its role in cardiac disease. The aim of this study was to investigate the clinical significance of SNX10 expression in AF. Methods Nineteen valvular heart disease patients with AF and nine valvular heart disease patients with sinus rhythm (SR) were enrolled. Atrial tissue samples from patients undergoing open heart surgery were examined. Atrial tissues of normal hearts were obtained from two cases’ autopsies. The SNX10 expression and its associations with the degree of fibrosis were analyzed by immunohistochemistry and Masson’s trichrome staining. Results SNX10 expression was detected in the cytoplasm of cardiac cells in human myocardial tissue. The SNX10 expression level was higher in the SR group than in the AF group ( P =0.023). SNX10 expression was negatively associated with the degree of fibrosis ( P =0.017, Spearman rho=-0.447), the New York Heart Association degree ( P =0.003, Spearman rho=-0.545), left atrial diameter ( P =0.038, Spearman rho=-0.393), right atrial diameter ( P =0.043, Spearman rho=-0.386), and the brain natriuretic peptide (BNP) level 24 hours after surgery ( P =0.030, Spearman rho=-0.426), but not the BNP level before surgery and 72 hours after surgery. No statistical significance was observed between SNX10 and the level of troponin T and C-reactive protein. Conclusion Decreased SNX10 might serve as a potential risk factor in AF of the valvular heart disease.

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“…SNX10 , a member of the family of sorting nexins, is a protein involved in intracellular protein sorting, trafficking, and signal transduction (36). Moreover, SNX10 has been reported to regulate endosomal morphology, which might be crucial for macrophage function, including phagocytosis and digestion of pathogens, inflammatory response, and Ag presentation (37). The SCNN1A gene encodes for the α subunit of the epithelial sodium channel (ENaC), which plays a critical role in the ion and fluid regulation of the lung.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Changes in Regional Lung Macrophages Are Associated with Metabolic Differences

et al. 2019

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A number of pulmonary diseases occur with upper lobe predominance, including cystic fibrosis and smoking-related chronic obstructive pulmonary disease. In the healthy lung, several physiologic and metabolic factors exhibit disparity when comparing the upper lobe of the lung to lower lobe, including differences in oxygenation, ventilation, lymphatic flow, pH, and blood flow. In this study, we asked whether these regional differences in the lung are associated with DNA methylation changes in lung macrophages that could potentially lead to altered cell responsiveness upon subsequent environmental challenge. All analyses were performed using primary lung macrophages collected via bronchoalveolar lavage from healthy human subjects with normal pulmonary function. Epigenome-wide DNA methylation was examined via Infinium MethylationEPIC (850K) array and validated by targeted next-generation bisulfite sequencing. We observed 95 CpG loci with significant differential methylation in lung macrophages, comparing upper lobe to lower lobe (all false discovery rate , 0.05). Several of these genes, including CLIP4, HSH2D, NR4A1, SNX10, and TYK2, have been implicated as participants in inflammatory/immune-related biological processes. Functionally, we identified phenotypic differences in oxygen use, comparing upper versus lower lung macrophages. Our results support a hypothesis that epigenetic changes, specifically DNA methylation, at a multitude of gene loci in lung macrophages are associated with metabolic differences regionally in lung. ImmunoHorizons, 2019, 3: 274-281.

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SNX10 promotes phagosome maturation in macrophages and protects mice againstListeria monocytogenesinfection

Cited by 23 publications

References 39 publications

SNX3 drives maturation of Borrelia phagosomes by forming a hub for PI(3)P, Rab5a, and galectin-9

SNX3 drives maturation of Borrelia phagosomes by forming a hub for PI(3)P, Rab5a, and galectin-9

Does Decreased SNX10 Serve as a Novel Risk Factor in Atrial Fibrillation of the Valvular Heart Disease? – A Case-Control Study

DNA Methylation Changes in Regional Lung Macrophages Are Associated with Metabolic Differences

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