Phenotype and Function of Myeloid-Derived Suppressor Cells Induced by Porphyromonas gingivalis Infection.

, a major etiologic agent of periodontitis, has been reported to induce the expansion of myeloid-derived suppressor cells (MDSC); however, little is known regarding the subpopulations of MDSC expanded by infection. Flow cytometry was used to evaluate bone marrow and spleen cells from mice infected with and controls for surface expression of CD11b, Ly6G, and Ly6C. To characterize the phenotype of MDSC subpopulations induced by infection, cells were sorted based on the differential expression of Ly6G and Ly6C. Moreover, since MDSC are suppressors of T cell immune activity, we determined the effect of the induced subpopulations of MDSC on the proliferative response of OVA-specific CD4 T cells. Lastly, the plasticity of MDSC to differentiate into osteoclasts was assessed by staining for tartrate-resistant acid phosphatase activity. infection induced the expansion of three subpopulations of MDSC (Ly6G Ly6C, Ly6G Ly6C, and Ly6G Ly6C); however, only CD11b Ly6G Ly6C-expressing cells exerted a significant suppressive effect on T cell proliferation. Inhibition of proliferative responses required T cell-MDSC contact and was mediated by inducible nitric oxide synthase and cationic amino acid transporter 2 via gamma interferon. Furthermore, only the CD11b Ly6G Ly6C subpopulation of MDSC induced by infection was able to differentiate into osteoclasts. Thus, the inflammatory response induced by infection promotes the expansion of immune-suppressive cells and consequently the development of regulatory inhibitors that curtail the host response. Moreover, monocytic MDSC have the plasticity to differentiate into OC, thus perhaps contributing to the OC pool in states of periodontal disease.