Sci Adv Jan , 2020Author(s):
Extreme pathophysiological stressors induce expansion of otherwise infrequent leukocyte populations. Here, we found a previously unidentified CD11bGr-1 myeloid cell population that expresses stem cell antigen-1 (Sca-1) induced upon experimental infection with . Although CD11bGr-1Sca-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 CD11bGr-1Sca-1 cells is dependent on IFN-γ in vivo, and in vitro stimulation of bone marrow cells or granulocyte-macrophage progenitors with IFN-γ generated CD11bGr-1Sca-1 cells. Depletion of CD11bGr-1Sca-1 cells by administrating anti-Sca-1 antibody strongly increased survival rates in an infection model by reducing organ damage and inflammatory cytokines. However, adoptive transfer of CD11bGr-1Sca-1 cells decreased survival rates by worsening the pathogenesis of infection. Together, we found a previously unidentified pathogenic CD11bGr-1Sca-1 population that plays an essential role in mortality during bacterial infection.