Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia

Recent studies have linked accumulation of the Gr-1(+) CD11b(+) cell phenotype with functional immunosuppression in diverse pathological conditions, including bacterial and parasitic infections and cancer. Gr-1(+) CD11b(+) cells were the largest population of cells present in the spleens of mice infected with sublethal doses of the Francisella tularensis live vaccine strain (LVS). In contrast, the number of T cells present in the spleens of these mice did not increase during early infection. There was a significant delay in the kinetics of accumulation of Gr-1(+) CD11b(+) cells in the spleens of B-cell-deficient mice, indicating that B cells play a role in recruitment and maintenance of this population in the spleens of mice infected with F. tularensis. The splenic Gr-1(+) CD11b(+) cells in tularemia were a heterogeneous population that could be further subdivided into monocytic (mononuclear) and granulocytic (polymorphonuclear) cells using the Ly6C and Ly6G markers and differentiated into antigen-presenting cells following ex vivo culture. Monocytic, CD11b(+) Ly6C(hi) Ly6G(-) cells but not granulocytic, CD11b(+) Ly6C(int) Ly6G(+) cells purified from the spleens of mice infected with F. tularensis suppressed polyclonal T-cell proliferation via a nitric oxide-dependent pathway. Although the monocytic, CD11b(+) Ly6C(hi) Ly6G(-) cells were able to suppress the proliferation of T cells, the large presence of Gr-1(+) CD11b(+) cells in mice that survived F. tularensis infection also suggests a potential role for these cells in the protective host response to tularemia.