Baquero Monica M, Plattner Brandon L
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
Front Immunol. 2017 May 22;8:534. doi: 10.3389/fimmu.2017.00534. eCollection 2017.
During early subspecies () infection, complex interactions occur between the bacteria, cells from the mononuclear phagocyte system (MPS) including both resident (macrophages and dendritic cells) and recruited (monocytes) cells, and other mucosal sentinel cells such as γδ T lymphocytes. Though the details of early host-pathogen interactions in cattle remain largely underexplored, our hypothesis is that these significantly influence development of host immunity and ultimate success or failure of the host to respond to infection. The aims of the present study were to first characterize monocyte-derived MPS cells from young calves with respect to their immunophenotype and function. Then, we set out to investigate the effects of WC1 and WC1 γδ T lymphocytes on (1) the differentiation of autologous monocytes and (2) the maturation of autologous monocyte-derived dendritic cells (MDDCs). To achieve this, peripheral blood WC1 or WC1 γδ T lymphocytes were cocultured with either autologous freshly isolated peripheral blood-derived monocytes or autologous immature MDDCs (iMDDCs). We began by measuring several markers of interest on MPS cells. Useful markers to distinguish monocyte-derived macrophages (MDMs) from MDDCs include CD11b, CD163, and CD172a, which are expressed significantly higher on MDMs compared with MDDCs. Function, but not phenotype, was influenced by WC1 γδ T lymphocytes: viability of harvested from monocytes differentiated in the presence of WC1 γδ T lymphocytes (dMonWC1) was significantly lower compared to MDMs and MDDCs. With respect to DC maturation, we first showed that mature MDDCs (mMDDCs) have significantly higher expression of CD11c, CD80, and CD86 compared with iMDDCs, and the phagocytic capacity of mMDDCs is significantly reduced compared to iMDDCs. We then showed that γδ T lymphocyte subsets induce functional (reduced phagocytosis) but not phenotypic (surface marker expression) iMDDC maturation. These data collectively show that γδ T lymphocytes influence differentiation, maturation, and ultimately the function of monocytes during infection, which has significant implications on survival of and success of host defense during early infection.
在早期亚种（）感染期间，细菌与单核吞噬细胞系统（MPS）的细胞（包括驻留细胞（巨噬细胞和树突状细胞）和募集细胞（单核细胞））以及其他黏膜哨兵细胞（如γδT淋巴细胞）之间会发生复杂的相互作用。尽管牛早期宿主 - 病原体相互作用的细节在很大程度上仍未得到充分研究，但我们的假设是，这些相互作用会显著影响宿主免疫的发展以及宿主对感染反应的最终成败。本研究的目的首先是根据免疫表型和功能对幼龄犊牛的单核细胞来源的MPS细胞进行表征。然后，我们着手研究WC1和WC1γδT淋巴细胞对（1）自体单核细胞分化和（2）自体单核细胞来源的树突状细胞（MDDCs）成熟的影响。为了实现这一目标，将外周血WC1或WC1γδT淋巴细胞与自体新鲜分离的外周血来源的单核细胞或自体未成熟MDDCs（iMDDCs）共培养。我们首先测量了MPS细胞上的几个感兴趣的标志物。区分单核细胞来源的巨噬细胞（MDMs）和MDDCs的有用标志物包括CD11b、CD163和CD172a，与MDDCs相比，它们在MDMs上的表达明显更高。功能而非表型受到WC1γδT淋巴细胞的影响：与MDMs和MDDCs相比，从在WC1γδT淋巴细胞存在下分化的单核细胞收获的（dMonWC1）的活力明显更低。关于DC成熟，我们首先表明，与iMDDCs相比，成熟的MDDCs（mMDDCs）的CD11c、CD80和CD86表达明显更高，并且与iMDDCs相比，mMDDCs的吞噬能力明显降低。然后我们表明，γδT淋巴细胞亚群诱导功能性（吞噬作用降低）而非表型性（表面标志物表达）的iMDDC成熟。这些数据共同表明，γδT淋巴细胞在感染期间影响单核细胞的分化、成熟以及最终功能，这对感染早期的存活和宿主防御的成功具有重要意义。
