Trang Karen, Raposo Rui André, Lowe Margaret M, Krow-Lucal Elisabeth R, Yonemoto Wes, Cabido Vinicius D, SenGupta Devi, McCune Joseph M
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
2 Department of Microbiology, Immunology and Tropical Medicine, The George Washington University , Washington, District of Columbia.
Viral Immunol. 2017 Apr;30(3):142-148. doi: 10.1089/vim.2016.0160. Epub 2017 Feb 2.
Among untreated HIV-infected pregnant women, the frequency of mother-to-child transmission of HIV is low (5-10%), with most infections occurring at or after birth. Given findings that fetal and adult monocytes are distinct from one another in terms of basal transcriptional profiles, and in phosphorylation of signal transducer and activators of transcription in response to cytokines, we hypothesized that fetal CD14+CD16- monocyte and monocyte-derived macrophages (MDMs) might, compared to their adult counterparts, express higher levels of transcripts for restriction factors and antiviral factors at baseline and/or after stimulation with cytokines that might be induced upon transmission of HIV in utero, for example, IFNα, IFNγ, and IL-6. We carried out these experiments and noted that a few genes, including APOBEC3B, APOBEC3C, and IFITM2, were expressed to a greater degree in fetal monocytes compared to adults. Similarly, the expression levels of APOBEC3F and TRIM32 were greater in fetal MDMs. However, most of these differences were not observed after stimulation with cytokines and the vast majority of antiviral genes were more highly expressed in adults. Therefore, the results of this study are not consistent with the hypothesis that increased expression of antiviral genes in fetal myeloid cells confers immune protection to fetuses in utero.
在未经治疗的感染HIV的孕妇中,HIV母婴传播的频率较低(5%-10%),大多数感染发生在出生时或出生后。鉴于有研究发现胎儿单核细胞和成人单核细胞在基础转录谱以及细胞因子刺激下信号转导和转录激活因子的磷酸化方面存在差异,我们推测与成人对应细胞相比,胎儿CD14+CD16-单核细胞和单核细胞衍生的巨噬细胞(MDM)在基线时和/或在用子宫内HIV传播时可能诱导产生的细胞因子(如IFNα、IFNγ和IL-6)刺激后,可能会表达更高水平的限制因子和抗病毒因子转录本。我们进行了这些实验,发现包括APOBEC3B、APOBEC3C和IFITM2在内的一些基因在胎儿单核细胞中的表达程度高于成人。同样,APOBEC3F和TRIM32在胎儿MDM中的表达水平更高。然而,在用细胞因子刺激后,这些差异大多未被观察到,并且绝大多数抗病毒基因在成人中表达更高。因此,本研究结果与胎儿髓系细胞中抗病毒基因表达增加可赋予子宫内胎儿免疫保护这一假设不一致。