Murine myeloid-derived suppressor cells are a source of elevated levels of interleukin-27 in early life and compromise control of bacterial infection
Murine myeloid-derived suppressor cells are a source of elevated levels of interleukin-27 in early life and compromise control of bacterial infection
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DOI：
10.1111/imcb.12224
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发表时间：
2019-05-01
影响因子：
4
通讯作者：
Robinson, Cory M.
中科院分区：
文献类型：
--
作者：
Gleave Parson, Madeline;Grimmett, Juanita;Robinson, Cory M.
生命早期的微生物感染仍然是全世界婴儿死亡的主要原因。这与该人群中的免疫缺陷一致。白细胞介素（IL）-27对多种免疫细胞类型具有抑制作用，我们已经证明，在人类和小鼠的生命早期，IL-27的产生是升高的。我们推测，IL-27水平升高对抗新生儿期感染的保护性反应。在这项研究中，我们扩展了先前在新生小鼠中的发现，以鉴定表达Gr-1的IL-27生产者群体，并根据表面标志物的表达和功能研究进一步鉴定为髓源性抑制细胞（MDSC）。在新生儿中，MDSC更丰富，并有助于该人群中IL-27的升高。虽然MDSC调节T淋巴细胞活化的能力已经被充分研究，但很少有研究调查MDSC对细菌感染期间先天免疫功能的影响。我们证明，巨噬细胞与MDSC共培养时，其控制大肠杆菌生长的能力受损。这种细菌是新生儿的一个重大问题，是细菌性败血症和脑膜炎的常见原因。MDSC对巨噬细胞功能的抑制作用由IL-27介导;包含中和IL-27的试剂促进了对细菌生长的改善控制。总之，这些结果表明，MDSC丰度的增加可能有助于早期对感染的易感性，并进一步强调IL-27的产生是抑制免疫的新型MDSC机制。
Microbial infections early in life remain a major cause of infant mortality worldwide. This is consistent with immune deficiencies in this population. Interleukin (IL)-27 is suppressive toward a variety of immune cell types, and we have shown that the production of IL-27 is elevated in humans and mice early in life. We hypothesize that elevated levels of IL-27 oppose protective responses to infection during the neonatal period. In this study, we extended previous findings in neonatal mice to identify a population of IL-27 producers that express Gr-1 and were further identified as myeloid-derived suppressor cells (MDSCs) based on the expression of surface markers and functional studies. In neonates, MDSCs are more abundant and contribute to the elevated pool of IL-27 in this population. Although the ability of MDSCs to regulate T lymphocyte activation has been well-studied, sparingly few studies have investigated the influence of MDSCs on innate immune function during bacterial infection. We demonstrate that macrophages are impaired in their ability to control growth of Escherichia coli when cocultured with MDSCs. This bacterium is a significant concern for neonates as a common cause of bacterial sepsis and meningitis. The suppressive effect of MDSCs on macrophage function is mediated by IL-27; inclusion of a reagent to neutralize IL-27 promotes improved control of bacterial growth. Taken together, these results suggest that the increased abundance of MDSCs may contribute to early life susceptibility to infection and further highlight production of IL-27 as a novel MDSC mechanism to suppress immunity.