دورية أكاديمية
Pseudomonas aeruginosa flagellar motility activates the phagocyte PI3K/Akt pathway to induce phagocytic engulfment.
| العنوان: | Pseudomonas aeruginosa flagellar motility activates the phagocyte PI3K/Akt pathway to induce phagocytic engulfment. |
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| المؤلفون: | Lovewell RR; Dept. of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Medical Center Dr., Lebanon, NH 03756. brent.berwin@dartmouth.edu., Hayes SM, O'Toole GA, Berwin B |
| المصدر: | American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2014 Apr 01; Vol. 306 (7), pp. L698-707. Date of Electronic Publication: 2014 Jan 31. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901229 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1504 (Electronic) Linking ISSN: 10400605 NLM ISO Abbreviation: Am J Physiol Lung Cell Mol Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society, c1989- |
| مواضيع طبية MeSH: | Macrophages, Alveolar/*immunology , Phagocytosis/*immunology , Phosphatidylinositol 3-Kinases/*physiology , Proto-Oncogene Proteins c-akt/*physiology , Pseudomonas aeruginosa/*physiology, Actins/metabolism ; Animals ; Flagella/physiology ; Mice ; Signal Transduction/immunology |
| مستخلص: | Phagocytosis of the bacterial pathogen Pseudomonas aeruginosa is the primary means by which the host controls bacterially induced pneumonia during lung infection. Previous studies have identified flagellar swimming motility as a key pathogen-associated molecular pattern (PAMP) recognized by phagocytes to initiate engulfment. Correspondingly, loss of flagellar motility is observed during chronic pulmonary infection with P. aeruginosa, and this likely reflects a selection for bacteria resistant to phagocytic clearance. However, the mechanism underlying the preferential phagocytic response to motile bacteria is unknown. Here we have identified a cellular signaling pathway in alveolar macrophages and other phagocytes that is specifically activated by flagellar motility. Genetic and biochemical methods were employed to identify that phagocyte PI3K/Akt activation is required for bacterial uptake and, importantly, it is specifically activated in response to P. aeruginosa flagellar motility. Based on these observations, the second important finding that emerged from these studies is that titration of the bacterial flagellar motility results in a proportional activation state of Akt. Therefore, the Akt pathway is responsive to, and corresponds with, the degree of bacterial flagellar motility, is independent of the actin polymerization that facilitates phagocytosis, and determines the phagocytic fate of P. aeruginosa. These findings elucidate the mechanism behind motility-dependent phagocytosis of extracellular bacteria and support a model whereby phagocytic clearance exerts a selective pressure on P. aeruginosa populations in vivo, which contributes to changes in pathogenesis during infections. |
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| معلومات مُعتمدة: | T32-GM-008704 United States GM NIGMS NIH HHS; R01-AI-003256 United States AI NIAID NIH HHS; P30 CA023108 United States CA NCI NIH HHS; T32-AI-07363 United States AI NIAID NIH HHS; AI-097694 United States AI NIAID NIH HHS; R01-AI-067405 United States AI NIAID NIH HHS; 1P30-RR-032136-01 United States RR NCRR NIH HHS |
| فهرسة مساهمة: | Keywords: Akt; Pseudomonas aeruginosa; flagellar motility; phagocytosis |
| المشرفين على المادة: | 0 (Actins) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20140204 Date Completed: 20140522 Latest Revision: 20211021 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3962627 |
| DOI: | 10.1152/ajplung.00319.2013 |
| PMID: | 24487390 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1504 |
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| DOI: | 10.1152/ajplung.00319.2013 |