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

  • Seunghan Han (Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Sungmin Moon (Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Youn Wook Chung (Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Ji-Hwan Ryu (Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine)
  • Received : 2023.04.14
  • Accepted : 2023.10.22
  • Published : 2023.10.31
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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 wildtype (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.

Keywords

Acknowledgement

This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2019M3A9B6066971 to J.-H.R.), and the Korea Mouse Phenotyping Project (2016M3A9D5A01952415 to J.-H.R.). This study was supported by a faculty research grant of Yonsei University College of Medicine (6-2017-0075 to J.-H.R.). We would like to thank Sang Sun Yoon (Yonsei University, Korea) for providing GFP-tagged S. aureus; In-Hong Choi (Yonsei University, Korea) for providing Ea.hy926 cell.

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