Malaria-specific Type 1 regulatory T cells are more abundant in first pregnancies and associated with placental malaria.
Malaria-specific Type 1 regulatory T cells are more abundant in first pregnancies and associated with placental malaria.
复制标题
DOI：
10.1016/j.ebiom.2023.104772
复制
发表时间：
2023-09
期刊：
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
妊娠期疟疾（MIP）导致较高的发病率，再次妊娠的妇女相比，多次妊娠的妇女，然而，这种妊娠依赖性保护的相关性和机制仍然不完全清楚。我们的目的是比较在疟疾流行地区的初孕和多次妊娠妇女之间的细胞免疫反应，并评估对MIP的保护相关性。我们利用RNA测序、流式细胞术和功能测定，对乌干达东部参加两项化学预防临床试验的203名初孕和多次妊娠孕妇的孕中期细胞免疫反应进行了表征。我们比较了不同妊娠期的反应，并确定了与妊娠期寄生虫血症和胎盘疟疾的相关性。使用全血RNA测序，未鉴定出总体上在经产妇（n = 12）和经产妇（n = 11）之间的显著差异表达基因（log 2（FC）> 2，FDR < 0.1）。然而，与多次妊娠妇女（n = 85）相比，再次妊娠妇女（n = 49）具有更高比例的疟疾特异性、非初始CD 4 + T细胞，其共表达IL-10和IFNγ（p = 0.000023），这些CD 4 + T细胞的百分比较高与妊娠期寄生虫血症的风险较高相关（Rs = 0.49，p = 0.001）和胎盘疟疾（p = 0.0073）。这些共产生IL-10和IFNγ的CD 4 + T细胞具有Tr 1细胞的基因组特征，包括转录因子cMAF和BATF以及细胞表面标记CTLA 4和LAG-3的表达。疟疾特异性Tr 1细胞在乌干达初产妇中高度流行，它们的存在与怀孕期间患疟疾的较高风险相关。了解Tr 1细胞的抑制是否在自然获得的妊娠依赖性免疫中起作用，可能有助于开发MIP的新疫苗或治疗方法。这项工作得到了（PO 1 HD 059454、U 01 AI 141308、U19 AI 089674、U 01 AI 155325、U 01 AI 150741）、（Basil奥康纳奖）和（A1113682）的资助。
Malaria in pregnancy (MIP) causes higher morbidity in primigravid compared to multigravid women; however, the correlates and mechanisms underlying this gravidity-dependent protection remain incompletely understood. We aimed to compare the cellular immune response between primigravid and multigravid women living in a malaria-endemic region and assess for correlates of protection against MIP. We characterised the second trimester cellular immune response among 203 primigravid and multigravid pregnant women enrolled in two clinical trials of chemoprevention in eastern Uganda, utilizing RNA sequencing, flow cytometry, and functional assays. We compared responses across gravidity and determined associations with parasitaemia during pregnancy and placental malaria. Using whole blood RNA sequencing, no significant differentially expressed genes were identified between primigravid (n = 12) and multigravid (n = 11) women overall (log 2(FC) > 2, FDR < 0.1). However, primigravid (n = 49) women had higher percentages of malaria-specific, non-naïve CD4+ T cells that co-expressed IL-10 and IFNγ compared with multigravid (n = 85) women (p = 0.000023), and higher percentages of these CD4+ T cells were associated with greater risks of parasitaemia in pregnancy (Rs = 0.49, p = 0.001) and placental malaria (p = 0.0073). These IL-10 and IFNγ co-producing CD4+ T cells had a genomic signature of Tr1 cells, including expression of transcription factors cMAF and BATF and cell surface makers CTLA4 and LAG-3. Malaria-specific Tr1 cells were highly prevalent in primigravid Ugandan women, and their presence correlated with a higher risk of malaria in pregnancy. Understanding whether suppression of Tr1 cells plays a role in naturally acquired gravidity-dependent immunity may aid the development of new vaccines or treatments for MIP. This work was funded by (PO1 HD059454, U01 AI141308, U19 AI089674, U01 AI155325, U01 AI150741), the (Basil O'Connor award), and the (OPP 1113682).
影响因子：
3.7
作者：
Knight AK;Dunlop AL;Kilaru V;Cobb D;Corwin EJ;Conneely KN;Smith AK
通讯作者：
Smith AK
DOI：
10.1186/s12958-021-00715-2
发表时间：
2021-02-24
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Son GH;Choi SY;Ju YJ;Lee KY;Lee JJ;Song JE;Kim Y;Park ST
通讯作者：
Park ST