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NADPH Oxidase 4-mediated Alveolar Macrophage Recruitment to Lung Attenuates Neutrophilic Inflammation in Staphylococcus aureus Infection

Moon Sungmin|Ryu Ji-Hwan|Han Seunghan|Chung Youn Wook
대한면역학회 (The Korean Association of Immunologists)|2023.10|Immune Network|제23권 제5호|pp. 1-21|DOI 10.4110/in.2023.23.e42

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키워드

Alveolar macrophageStaphylococcus aureusBacterial infectionsNADPH oxidase 4

초록

When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during Staphylococcus aureus lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to S. aureus infection compared to wild-type (WT) mice. Interestingly, the burden of S. aureus in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during S. aureus infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute S. aureus infection.

Abstract

When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during Staphylococcus aureus lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to S. aureus infection compared to wild-type (WT) mice. Interestingly, the burden of S. aureus in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during S. aureus infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute S. aureus infection.

참고문헌 (56)

  1. Aberdein JD, "Alveolar macrophages in pulmonary host defence the unrecognized role of apoptosis as a mechanism of intracellular bacterial killing", Clin Exp Immunol, 174, pp.193~202 (2013)
  2. Hussell T, "Alveolar macrophages : plasticity in a tissue-specific context", Nat Rev Immunol, 14, pp.81~93 (2014)
  3. Mathie SA, "Alveolar macrophages are sentinels of murine pulmonary homeostasis following inhaled antigen challenge", Allergy, 70, pp.80~89 (2015)
  4. Shi C, "Monocyte recruitment during infection and inflammation", Nat Rev Immunol, 11, pp.762~774 (2011)
  5. Regal-McDonald K, "High-mannose intercellular adhesion molecule-1 enhances CD16+ monocyte adhesion to the endothelium", Am J Physiol Heart Circ Physiol, 317, pp.H1028~H1038 (2019)
  6. Lin YT, "Visfatin promotes monocyte adhesion by upregulating ICAM-1 and VCAM-1 expression in endothelial cells via activation of p38-PI3K-Akt signaling and subsequent ROS production and IKK", NF-κb activation, 2019, pp.52, 1398~1411
  7. McQuattie-Pimentel AC, "Monocyte-derived alveolar macrophages : the dark side of lung repair?", Am J Respir Cell Mol Biol, 58, pp.5~6 (2018)
  8. Allard B, "Alveolar macrophages in the resolution of inflammation, tissue repair, and tolerance to infection", Front Immunol, 9, pp.1777~ (2018)
  9. Das A, "Monocyte and macrophage plasticity in tissue repair and regeneration", Am J Pathol, 185, pp.2596~2606 (2015)
  10. Westphalen K, "Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity", Nature, 506, pp.503~506 (2014)
  11. Jain S, "Community-acquired pneumonia requiring hospitalization among U. S. children", N Engl J Med, 372, pp.835~845 (2015)
  12. Ryu JC, "Neutrophil pyroptosis mediates pathology of P. aeruginosa lung infection in the absence of the NADPH oxidase NOX2", Mucosal Immunol, 10, pp.757~774 (2017)
  13. Self WH, "Staphylococcus aureus community-acquired pneumonia : prevalence, clinical characteristics, and outcomes", Clin Infect Dis, 63, pp.300~309 (2016)
  14. Buvelot H, "Staphylococcus aureus, phagocyte NADPH oxidase and chronic granulomatous disease", FEMS Microbiol Rev, 41, pp.139~157 (2017)
  15. Wertheim HF, "The role of nasal carriage in Staphylococcus aureus infections", Lancet Infect Dis, 5, pp.751~762 (2005)
  16. Parker D, "Immunopathogenesis of Staphylococcus aureus pulmonary infection", Semin Immunopathol, 34, pp.281~297 (2012)
  17. DeLeo FR, "Host defense and pathogenesis in Staphylococcus aureus infections", Infect Dis Clin North Am, 23, pp.17~34 (2009)
  18. Bernard K, "NADPH oxidases in lung health and disease", Antioxid Redox Signal, 20, pp.2838~2853 (2014)
  19. Basuroy S, "Nox4 NADPH oxidase-derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-α-induced apoptosis", Am J Physiol Cell Physiol, 300, pp.C256~C265 (2011)
  20. Martyn KD, "Functional analysis of NOX4 reveals unique characteristics compared to other NADPH oxidases", Cell Signal, 18, pp.69~82 (2006)
  21. Pendyala S, "Role of NOX4 and NOX2 in hyperoxia-induced reactive oxygen species generation and migration of human lung endothelial cells", Antioxid Redox Signal, 11, pp.747~764 (2009)
  22. Kim J, "Flagellin-induced NADPH oxidase 4 activation is involved in atherosclerosis", Sci Rep, 6, pp.25437~ (2016)
  23. Moon JS, "NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages", Nat Med, 22, pp.1002~1012 (2016)
  24. Kim JH, "NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection", Sci Rep, 7, pp.6361~ (2017)
  25. Fu P, "Role of nicotinamide adenine dinucleotide phosphate-reduced oxidase proteins in Pseudomonas aeruginosa-induced lung inflammation and permeability", Am J Respir Cell Mol Biol, 48, pp.477~488 (2013)
  26. Neupane AS, "Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis", Cell, 183, pp.110~125 (2020)
  27. McDonald KR, "Hydrogen peroxide regulates endothelial surface N-glycoforms to control inflammatory monocyte rolling and adhesion", Redox Biol, 34, pp.101498~ (2020)
  28. Walpola PL, "Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress", Arterioscler Thromb Vasc Biol, 15, pp.2~10 (1995)
  29. Usui T, "VEGF164(165)as the pathological isoform : differential leukocyte and endothelial responses through VEGFR1 and VEGFR2", Invest Ophthalmol Vis Sci, 45, pp.368~374 (2004)
  30. Kim I, "Vascular endothelial growth factor expression of intercellular adhesion molecule 1(ICAM-1), vascular cell adhesion molecule 1(VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells", J Biol Chem, 276, pp.7614~7620 (2001)
  31. Radisavljevic Z, "Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase", AKT, J Biol Chem, pp.2000, 275[DOI]
  32. Kim YM, "ROS-induced ROS release orchestrated by NOX4, NOX2, and mitochondria in VEGF signaling and angiogenesis", Am J Physiol Cell Physiol, 312, pp.C749~C764 (2017)
  33. Miyano K, "The NADPH oxidase NOX4 promotes the directed migration of endothelial cells by stabilizing vascular endothelial growth factor receptor 2 protein", J Biol Chem, 295, pp.11877~11890 (2020)
  34. Steiner DJ, "Detrimental influence of alveolar macrophages on protective humoral immunity during francisella tularensis schus4 pulmonary infection", Infect Immun, 86 (2018)
  35. Van Buul JD, "Expression and localization of NOX2 and NOX4 in primary human endothelial cells", Antioxid Redox Signal, 7, pp.308~317 (2005)
  36. Ago T, "NOX4 as the major catalytic component of an endothelial NAD(P)H oxidase", Circulation, 109, pp.227~233 (2004)
  37. Carnesecchi S, "A key role for NOX4 in epithelial cell death during development of lung fibrosis", Antioxid Redox Signal, 15, pp.607~619 (2011)
  38. Kim HJ, "The role of NOX4 in oxidative stress-induced MUC5AC overexpression in human airway epithelial cells", Am J Respir Cell Mol Biol, 39, pp.598~609 (2008)
  39. Lee CF, "Regulation of monocyte adhesion and migration by nox4", PLoS One, 8, pp.e66964~ (2013)
  40. Ullevig S, "NADPH oxidase 4 mediates monocyte priming and accelerated chemotaxis induced by metabolic stress", Arterioscler Thromb Vasc Biol, 32, pp.415~426 (2012)
  41. Fu P, "Nox4 mediates Pseudomonas aeruginosa-induced nuclear reactive oxygen species generation and chromatin remodeling in lung epithelium", Antioxidants, 10, pp.477~ (2021)
  42. Kevil CG, "Essential role of ICAM-1 in mediating monocyte adhesion to aortic endothelial cells", Am J Physiol Cell Physiol, 281, pp.C1442~C1447 (2001)
  43. Yang L, "ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow", Blood, 106, pp.584~592 (2005)
  44. Sumagin R, "Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing", Mucosal Immunol, 9, pp.1151~1162 (2016)
  45. Regal-McDonald K, "Selective recruitment of monocyte subsets by endothelial n-glycans", Am J Pathol, 190, pp.947~957 (2020)
  46. Scott DW, "Identification of a high-mannose ICAM-1 glycoform : effects of ICAM-1 hypoglycosylation on monocyte adhesion and outside in signaling", Am J Physiol Cell Physiol, 305, pp.C228~C237 (2013)
  47. Mizgerd JP, "Molecular mechanisms of neutrophil recruitment elicited by bacteria in the lungs", Semin Immunol, 14, pp.123~132 (2002)
  48. Vieira SM, "A crucial role for TNF-alpha in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC", CXCL1 and LIX, Br J Pharmacol, pp.2009, 158[DOI]
  49. Zasłona Z, "Transcriptome profiling of primary murine monocytes, lung macrophages and lung dendritic cells reveals a distinct expression of genes involved in cell trafficking", Respir Res, 10, pp.2~ (2009)
  50. Schagat TL, "Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils", J Immunol, 166, pp.2727~2733 (2001)
  51. Wong CK, "Aging impairs alveolar macrophage phagocytosis and increases influenza-induced mortality in mice", J Immunol, 199, pp.1060~1068 (2017)
  52. Serhan CN, "Lipid mediators in the resolution of inflammation", Cold Spring Harb Perspect Biol, 7, pp.a016311~ (2014)
  53. Knapp S, "Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia", Am J Respir Crit Care Med, 167, pp.171~179 (2003)
  54. Hou F, "Diversity of macrophages in lung homeostasis and diseases", Front Immunol, 12, pp.753940~ (2021)
  55. Puttur F, "Airway macrophages as the guardians of tissue repair in the lung", Immunol Cell Biol, 97, pp.246~257 (2019)
  56. Aegerter H, "Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection", Nat Immunol, 21, pp.145~157 (2020)

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