CD11b+ Ly6Chi Ly6G- immature myeloid cells recruited in response to Salmonella enterica serovar Typhimurium infection exhibit protective and immunosuppressive properties.

ABSTRACT

Immature myeloid cells in bone marrow are a heterogeneous population of cells that, under normal conditions, provide tissues with protective cell types such as granulocytes and macrophages. Under certain pathological conditions, myeloid cell homeostasis is altered and immature forms of these cells appear in tissues. Murine immature myeloid cells that express CD11b and Ly6C or Ly6G (two isoforms of Gr-1) have been associated with immunosuppression in cancer (in the form of myeloid-derived suppressor cells) and, more recently, infection. Here, we found that CD11b(+) Ly6C(hi) Ly6G(-) and CD11b(+) Ly6C(int) Ly6G(+) cells accumulated and persisted in tissues of mice infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). Recruitment of CD11b(+) Ly6C(hi) Ly6G(-) but not CD11b(+) Ly6C(int) Ly6G(+) cells from bone marrow into infected tissues depended on chemokine receptor CCR2. The CD11b(+) Ly6C(hi) Ly6G(-) cells exhibited a mononuclear morphology, whereas the CD11b(+) Ly6C(int) Ly6G(+) cells exhibited a polymorphonuclear or band-shaped nuclear morphology. The CD11b(+) Ly6C(hi) Ly6G(-) cells differentiated into macrophage-like cells following ex vivo culture and could present antigen to T cells in vitro. However, significant proliferation of T cells was observed only when the ability of the CD11b(+) Ly6C(hi) Ly6G(-) cells to produce nitric oxide was blocked. CD11b(+) Ly6C(hi) Ly6G(-) cells recruited in response to S. Typhimurium infection could also present antigen to T cells in vivo, but increasing their numbers by adoptive transfer did not cause a corresponding increase in T cell response. Thus, CD11b(+) Ly6C(hi) Ly6G(-) immature myeloid cells recruited in response to S. Typhimurium infection exhibit protective and immunosuppressive properties that may influence the outcome of infection.