Function of Siglec 5 in T cell activation.

B群链球菌(GBS)是健康成人常见的共生菌。约20%的 妇女在无症状的情况下在生殖道感染GBS。然而，GBS可能会导致严重的 新生儿中的疾病。大多数来自殖民妇女的新生儿感染了GBS，并且 这些婴儿中约有1%会患上败血症。事实上，GBS是婴儿侵袭性感染的主要原因。GBS 感染对早产儿来说可能是致命的。此外，大约50%的GBS脑膜炎幸存者遭受 终生神经损伤。因此，了解GBS如何在婴儿和 是什么导致了GBS的侵袭性感染，以改善新生儿的卫生保健。 婴儿的免疫系统受到抑制，这使他们非常容易受到感染和限制 他们对保护性和救命性疫苗的免疫反应。获得性免疫反应和先天免疫反应 婴儿的效果不如成人。然而，婴儿免疫与成人免疫的不同之处在于 作为替补，需要更多的调查。 GBS具有调节人类免疫系统的独特能力。一种这样的机制是 GBS细胞壁锚定β蛋白的免疫抑制作用。这种蛋白质与补体调节结合。 因子H和IgA的恒定区。此外，gbsβ蛋白与C型唾液酸结合 免疫球蛋白样凝集素5(Siglec)5。Siglec 5是一种多种类型的髓系细胞表达的细胞表面蛋白 具有两个免疫抑制基序的细胞质结构域：基于免疫受体酪氨酸 抑制基序(ITIM)和免疫受体酪氨酸开关基序(ITSM)。签名5被显示为 抑制中性粒细胞和巨噬细胞的激活，但以前未见人T细胞表达的报道 细胞。重要的是，我们的序列比对分析表明，Siglec 5的细胞质区域与 与原型免疫检查点分子PD-1有关。 为了测试GBS是否通过β蛋白-Siglec 5相互作用调节围产期免疫反应，我们研究了 脐血细胞表达Siglec-5的初步研究与之前的报告不同，我们的数据显示 大多数活化的脐带血和成人血T细胞表达Siglec 5。 LINE抑制抗原受体诱导的转录因子的激活。此外，重组gbsβ 蛋白质抑制主要的T细胞反应，特别是Th1型细胞因子的产生。因此，Siglec 5是一种 潜在的免疫检查点分子，以前没有被识别。 基于这些数据，我们假设GBS在感染β时抑制围产期T细胞的激活 蛋白质-Siglec 5相互作用，减少适应性免疫反应。在这项研究中，我们的目标是追求 以下是两个问题。(1)gbsβ蛋白如何改变T细胞的激活？(2)Siglec 5是必需的吗？ GBS-β蛋白对T细胞的抑制作用

Group B Streptococcus (GBS ) is a common commensal bacterium for healthy adults. Approximately 20% of women are infected with GBS in the genitourinary tract without symptoms. However, GBS can cause serious disease in newborn infants. A majority of newborn infants from colonized women get infected with GBS, and about 1% of these infants develop sepsis. Indeed, GBS is a leading cause of invasive infections in infants. GBS infection can be lethal for preterm babies. Moreover, approximately 50% of GBS meningitis survivors suffer lifelong neurological impairment. Thus, it is critically important to understand how GBS colonizes infants and what causes invasive infection by GBS to improve the health care of newborns. Infants have a suppressed immune system which makes them highly vulnerable to infections and limits their immune responses to protective and life-saving vaccines. Both adaptive and innate immune responses in the infant are less effective than those in adult. However, how infant immunity differs from adult immunity in understudies and requires more investigations. GBS has unique capabilities to modulate the human immune system. One such mechanism is the immune inhibition by GBS's cell wall-anchored β–protein. This protein binds to a complement regulatory factor H and the constant region of IgA. Moreover, the GBS β protein binds a C-type Sialic acid-binding immunoglobulin-like lectin 5 (Siglec) 5. Siglec 5 is a cell surface protein expressed by many types of myeloid cells and has a cytoplasmic domain with two immunosuppressive motifs: immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM). Siglec 5 was shown to suppress activation of neutrophils and macrophages but was reported previously not expressed by human T cells. Importantly, our sequence alignment analysis showed that the cytoplasmic region of Siglec 5 is closely related to a prototypic immune checkpoint molecule PD-1. To test if GBS modulates perinatal immune responses by β protein-Siglec 5 interactions, we examined the expression of Siglec 5 by cord blood cells in our preliminary study. Unlike previous reports, our data show that a majority of activated cord blood and adult blood T cells express Siglec 5. Siglec 5 expressions in a T cell line inhibited antigen receptor-induced activation of transcription factors. Moreover, recombinant GBS β protein suppressed primary T cell responses, especially Th1 type cytokine productions. Thus, Siglec 5 is a potential immune checkpoint molecule that was not previously recognized. Based on these data, we hypothesize that GBS inhibits activation of perinatal T cells upon infection by β protein-Siglec 5 interactions and reduces adaptive immune responses. In this study, we aim to pursue the following two questions. (1) How does the GBS β protein change T cell activation? (2) Is Siglec 5 required for the T cell suppression by GBS-β protein?