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  • 제21권2호
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  • Pages.13.1-13.19
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  • 2021
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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CD11b Deficiency Exacerbates Methicillin-Resistant Staphylococcus aureus-Induced Sepsis by Upregulating Inflammatory Responses of Macrophages

  • Hyunsub Sim (Department of Biomedical Science, College of Natural Science, Hallym University) ;
  • Daecheol Jeong (Department of Biomedical Science, College of Natural Science, Hallym University) ;
  • Hye-In Kim (Department of Biomedical Science, College of Natural Science, Hallym University) ;
  • Seongwon Pak (Department of Biomedical Science, College of Natural Science, Hallym University) ;
  • Bikash Thapa (Institute of Bioscience and Biotechnology, Hallym University) ;
  • Hyung-Joo Kwon (Department of Microbiology, College of Medicine, Hallym University) ;
  • Keunwook Lee (Department of Biomedical Science, College of Natural Science, Hallym University)
  • 투고 : 2020.08.19
  • 심사 : 2021.01.07
  • 발행 : 2021.04.30
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초록

Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

키워드

과제정보

This research was supported by Korean Mouse Phenotyping Project (NRF-2014M3A9D5A01073841) funded by the Ministry of Science and ICT through the National Research Foundation, Basic Science Research Program (NRF-2018R1D1A1B07048260; NRF-2019R1A6A1A11036849) funded by the Ministry of Education through the National Research Foundation, and the Hallym University Specialization Fund (HRF-S-12).

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