PLoS Pathogens:HIV或在肠道中隐藏而免于被杀灭
Bioon · 2014/09/02
加州大学戴维斯分校的研究人员通过研究发现:HIV或许可以隐藏在肠道中而免于被机体免疫系统清除;研究者在对猿猴免疫缺损病毒(SIV)进行研究后发现,肠道中的特殊细胞—潘氏细胞会对病毒的侵入产生早期反应,而其也可以通过产生白细胞介素-1β(IL-1β)来引发肠炎反应。


近日,来自加州大学戴维斯分校的研究人员通过研究发现,HIV或许可以隐藏在肠道中而免于被机体免疫系统清除;研究者在对猿猴免疫缺损病毒(SIV)进行研究后发现,肠道中的特殊细胞—潘氏细胞会对病毒的侵入产生早期反应,而其也可以通过产生白细胞介素-1β(IL-1β)来引发肠炎反应,相关研究成果刊登于国际杂志PLoS Pathogens上。在SIV病毒存在的情况下,IL-1β可以促使肠道上皮细胞破坏来为保护机体抵御SIV的感染,研究者表示,目前完全清除病毒且恢复机体免疫力的最大障碍就是肠道中存在稳定的HIV病毒库,而关于早期病毒侵袭及其如何在肠道中建立病毒库研究人员却知之甚少。

研究者Satya Dandekar表示,我们想去揭示是什么使得HIV病毒侵袭肠道,从而引发炎性反应并且杀死免疫细胞,这项研究中我们发现潘氏细胞或许就是肠道中HIV最开始感染的传感器,进而其会引发肠炎、组织损伤及病毒感染的扩散,我们的研究发现也为揭示阻断病毒早期感染的潜在的靶点及新型干预策略提供新的思路。

文章中,研究人员对最开始感染2.5天的一系列肠道SIV细胞进行了检测,对病毒产生的炎性反应主要发生在肠道壁上,研究者发现IL-1β降低了紧密连接蛋白的产量,后者对于产生肠道抵御病毒感染的保护屏障至关重要。随着研究的深入,研究者还发现,通过IL-1β产生的炎性反应或许是从潘氏细胞开始的,在病毒感染早期,潘氏细胞感知SIV的感染和IL-1β的产涩会难过和肠道上皮细胞的损伤存在一定的关联。

研究者表示,将一种益生菌—植物乳杆菌加入到肠道中后可以逆转因IL-1β水平降低而引发的肠道损伤,从而使得炎症恢复并且加速修复肠道组织;这项研究揭示了,利用寄生菌的协同作用或许可以有效干扰病毒的早期感染和扩散;当然揭示益生菌在肠道免疫反应中的作用对于开发病毒感染的疗法也非常重要。

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  • Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption

    HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to the CD4+ T cell depletion, are not known. Further, the impact of early viral infection on mucosal responses to pathogenic and commensal microbes has not been investigated. We utilized the SIV model of AIDS to assess the earliest host-virus interactions and mechanisms of inflammation and dysfunction in the gut, prior to CD4+ T cell depletion. An intestinal loop model was used to interrogate the effects of SIV infection on gut mucosal immune sensing and response to pathogens and commensal bacteria in vivo. At 2.5 days post-SIV infection, low viral loads were detected in peripheral blood and gut mucosa without CD4+ T cell loss. However, immunohistological analysis revealed the disruption of the gut epithelium manifested by decreased expression and mislocalization of tight junction proteins. Correlating with epithelial disruption was a significant induction of IL-1β expression by Paneth cells, which were in close proximity to SIV-infected cells in the intestinal crypts. The IL-1β response preceded the induction of the antiviral interferon response. Despite the disruption of the gut epithelium, no aberrant responses to pathogenic or commensal bacteria were observed. In fact, inoculation of commensal Lactobacillus plantarum in intestinal loops led to rapid anti-inflammatory response and epithelial tight junction repair in SIV infected macaques. Thus, intestinal Paneth cells are the earliest responders to viral infection and induce gut inflammation through IL-1β signaling. Reversal of the IL-1β induced gut epithelial damage by Lactobacillus plantarum suggests synergistic host-commensal interactions during early viral infection and identify these mechanisms as potential targets for therapeutic intervention.

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