CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS
CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS
复制标题
CD24和Fc融合蛋白可保护SIVmac239感染的中国恒河猴免于进展为艾滋病
DOI：
10.1016/j.antiviral.2018.07.004
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发表时间：
2018-09-01
影响因子：
7.6
通讯作者：
Zheng, Yong-Tang
中科院分区：
文献类型：
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作者：
Tian, Ren-Rong;Zhang, Ming-Xu;Zheng, Yong-Tang
慢性免疫激活和全身性炎症是获得性免疫缺陷综合征（艾滋病）的潜在原因。据报道，病毒复制和微生物易位的产物、共同感染或机会性病原体以及危险相关的分子模式有助于人类免疫缺陷病毒1型/猴免疫缺陷病毒（HIV-1/SIV）感染或其他疾病的慢性免疫激活和炎症。为了开发HIV-1/AIDS的新策略和治疗方法，我们测试了CD24和Fc融合蛋白（CD24Fc）是否可以保护SIV感染的中国恒河猴（ChRMs）。CD24Fc与危险相关的分子模式和唾液酸结合的igg样凝集素相互作用，以减轻炎症。我们发现CD24Fc治疗降低了体重减轻、消瘦综合征、顽固性腹泻和艾滋病发病率和死亡率，同时对siv感染动物具有良好的耐受性。与顽固性腹泻的消除相对应，CD24Fc通过降低炎症细胞、病理评分和炎症因子表达，显著降低外周血单核细胞IL-6和吲哚胺2,3 -双加氧酶-1的表达以及回肠、结肠和直肠的炎症。此外，尽管CD24Fc没有恢复CD4(+) T细胞数量或显著改变T细胞亚群或CD4(+) T细胞活化，但它维持了外周血单核细胞和骨髓中低水平的血浆可溶性CD14、CD8(+) T细胞活化、病毒载量和前病毒载量。这些结果表明，CD24Fc可以保护siv感染的chrm不发展为艾滋病。这也暗示CD24Fc可能是控制HIV-1/AIDS的潜在治疗方法。
Chronic immune activation and systemic inflammation are underlying causes of acquired immunodeficiency syndrome (AIDS). Products of virus replication and microbial translocation, co-infection or opportunistic pathogens, and danger-associated molecular patterns have been reported to contribute to chronic immune activation and inflammation in human immunodeficiency virus type-1/simian immunodeficiency virus (HIV-1/SIV) infection or other disease. To develop new strategies and therapies for HIV-1/AIDS, we tested if the CD24 and Fc fusion protein (CD24Fc), which interacts with danger-associated molecular patterns and sialic acid binding Ig-like lectin to attenuate inflammation, can protect Chinese rhesus macaques (ChRMs) with SIV infection. We found that CD24Fc treatment decreased weight loss, wasting syndrome, intractable diarrhea, and AIDS morbidity and mortality, while it was well tolerated by SIV-infected animals. Corresponding to the elimination of intractable diarrhea, CD24Fc significantly reduced the expression of IL-6 and indoleamine 2, 3-dioxygenase-1 in peripheral blood mononuclear cell and inflammation in the ileum, colon and rectum based on the reduction of inflammatory cells, pathological scores and expression of inflammatory cytokines. Furthermore, although CD24Fc did not restore CD4(+) T cell number or significantly change T cell subsets or CD4(+) T cell activation, it maintained low levels of plasma soluble CD14, CD8(+) T cell activation, viral load and proviral load in the peripheral blood mononuclear cells and marrow. These results suggested that CD24Fc confers protection to SIV-infected ChRMs against progression to AIDS. It was also implied that CD24Fc may be a potential therapeutic approach for the control of HIV-1/AIDS.