Journal
SCIENCE ADVANCES
Volume 6, Issue 4, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax8820
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2015R1A2A1A10054567, NRF-2017R1A5A1014560, NRF-2018R1A2B3003868]
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Extreme pathophysiological stressors induce expansion of otherwise infrequent leukocyte populations. Here, we found a previously unidentified CD11b(+)Gr-1(+) myeloid cell population that expresses stem cell antigen-1 (Sca-1) induced upon experimental infection with Staphylococcus aureus. Although CD11b(+)Gr-1(+)Sca-1(+) cells have impaired migratory capacity and superoxide anion-producing activity, they secrete increased levels of several cytokines and chemokines compared to Sca-1(-) counterparts. The generation of CD11b(+)Gr-1(+)Sca-1(+) cells is dependent on IFN-gamma in vivo, and in vitro stimulation of bone marrow cells or granulocyte-macrophage progenitors with IFN-gamma generated CD11b(+)Gr-1(+)Sca-1(+) cells. Depletion of CD11b(+)Gr-1(+)Sca-1(+) cells by administrating anti-Sca-1 antibody strongly increased survival rates in an S. aureus infection model by reducing organ damage and inflammatory cytokines. However, adoptive transfer of CD11b(+)Gr-1(+)Sca-1(+) cells decreased survival rates by worsening the pathogenesis of S. aureus infection. Together, we found a previously unidentified pathogenic CD11b(+)Gr-1(+)Sca-1(+) population that plays an essential role in mortality during bacterial infection.
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