Su Lingkai, Xu Qingan, Zhang Ping, Michalek Suzanne M, Katz Jannet
Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, Alabama, USA.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Infect Immun. 2017 Jul 19;85(8). doi: 10.1128/IAI.00213-17. Print 2017 Aug.
, 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.
据报道，牙周炎的主要病原体——牙龈卟啉单胞菌可诱导髓源性抑制细胞（MDSC）扩增；然而，关于牙龈卟啉单胞菌感染所扩增的MDSC亚群知之甚少。采用流式细胞术评估感染牙龈卟啉单胞菌的小鼠和对照小鼠的骨髓和脾细胞中CD11b、Ly6G和Ly6C的表面表达。为了表征感染诱导的MDSC亚群的表型，根据Ly6G和Ly6C的差异表达对细胞进行分选。此外，由于MDSC是T细胞免疫活性的抑制剂，我们确定了诱导的MDSC亚群对OVA特异性CD4 T细胞增殖反应的影响。最后，通过抗酒石酸酸性磷酸酶活性染色评估MDSC向破骨细胞分化的可塑性。牙龈卟啉单胞菌感染诱导了三个MDSC亚群（Ly6G⁻Ly6C⁺、Ly6G⁻Ly6C⁻和Ly6G⁺Ly6C⁻）的扩增；然而，只有表达CD11b⁺Ly6G⁻Ly6C⁺的细胞对T细胞增殖具有显著的抑制作用。增殖反应的抑制需要T细胞与MDSC接触，并通过诱导型一氧化氮合酶和阳离子氨基酸转运体2经由γ干扰素介导。此外，只有牙龈卟啉单胞菌感染诱导的MDSC的CD11b⁺Ly6G⁻Ly6C⁺亚群能够分化为破骨细胞。因此，牙龈卟啉单胞菌感染诱导的炎症反应促进了免疫抑制细胞的扩增，并因此促进了抑制宿主反应的调节性抑制剂的产生。此外，单核细胞MDSC具有分化为破骨细胞的可塑性，因此可能在牙周疾病状态下对破骨细胞池有贡献。
