Novel CD11b⁺Gr-1⁺Sca-1⁺ myeloid cells drive mortality in bacterial infection.

Abstract

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 <i>Staphylococcus aureus</i>. 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-γ in vivo, and in vitro stimulation of bone marrow cells or granulocyte-macrophage progenitors with IFN-γ 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 <i>S. aureus</i> 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 <i>S. aureus</i> infection. Together, we found a previously unidentified pathogenic CD11b⁺Gr-1⁺Sca-1⁺ population that plays an essential role in mortality during bacterial infection.