Indoleamine 2,3-dioxygenase 1 regulates cell permissivity to astrovirus infection.
Indoleamine 2,3-dioxygenase 1 regulates cell permissivity to astrovirus infection.
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DOI：
10.1016/j.mucimm.2023.05.011
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发表时间：
2023-08
影响因子：
8
通讯作者：
Schultz-Cherry, Stacey
中科院分区：
文献类型：
--
作者：
Cortez, Valerie;Livingston, Brandi;Sharp, Bridgett;Hargest, Virginia;Papizan, James B.;Pedicino, Natalie;Lanning, Sarah;Jordan, Summer Vaughn;Gulman, Jacob;Vogel, Peter;Dubois, Rebecca M.;Crawford, Jeremy Chase;Boyd, David F.;Pruett-Miller, Shondra M.;Thomas, Paul G.;Schultz-Cherry, Stacey
星状病毒引起一系列疾病，从无症状感染到严重腹泻，但对其发病机制知之甚少。我们先前确定小肠杯状细胞是小鼠星状病毒-1感染的主要细胞类型。在这里，我们专注于宿主对感染的免疫反应，无意中发现了吲哚胺2，3-双加氧酶1（Ido 1），一种宿主色氨酸分解酶，在小鼠和人类星状病毒的细胞嗜性中的作用。我们发现，Ido 1的表达是高度富集的感染杯状细胞，并在空间上对应于感染的分区。由于Ido 1可以作为炎症的负调节因子，我们假设它可以抑制宿主的抗病毒反应。尽管在杯状细胞以及簇状细胞和肠上皮细胞旁观者中存在强大的干扰素信号传导，但我们观察到延迟的细胞因子诱导和粪便脂质运载蛋白-2水平的抑制。虽然我们发现IDO−/−动物对感染的抵抗力更强，但这与杯状细胞减少无关，也不能通过敲除干扰素反应来拯救，这表明IDO 1反而调节细胞增殖。我们对IDO 1 −/− Caco-2细胞进行了表征，并观察到人类星状病毒-1感染显著减少。总之，这项研究强调了Ido 1在星形病毒感染和上皮细胞成熟中的作用。
Astroviruses cause a spectrum of diseases spanning asymptomatic infections to severe diarrhea, but little is understood about their pathogenesis. We previously determined that small intestinal goblet cells were the main cell type infected by murine astrovirus-1. Here, we focused on the host immune response to infection and inadvertently discovered a role for indoleamine 2,3-dioxygenase 1 (Ido1), a host tryptophan catabolizing enzyme, in the cellular tropism of murine and human astroviruses. We identified that Ido1 expression was highly enriched among infected goblet cells, and spatially corresponded to the zonation of infection. Because Ido1 can act as a negative regulator of inflammation, we hypothesized it could dampen host antiviral responses. Despite robust interferon signaling in goblet cells, as well as tuft cell and enterocyte bystanders, we observed delayed cytokine induction and suppressed levels of fecal lipocalin-2. Although we found Ido−/− animals were more resistant to infection, this was not associated with fewer goblet cells nor could it be rescued by knocking out interferon responses, suggesting that IDO1 instead regulates cell permissivity. We characterized IDO1−/− Caco-2 cells and observed significantly reduced human astrovirus-1 infection. Together this study highlights a role for Ido1 in astrovirus infection and epithelial cell maturation.
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影响因子：
3.7
作者：
Chassaing B;Srinivasan G;Delgado MA;Young AN;Gewirtz AT;Vijay-Kumar M
通讯作者：
Vijay-Kumar M
影响因子：
5.4
作者：
Cortez, Valerie;Sharp, Bridgett;Schultz-Cherry, Stacey
通讯作者：
Schultz-Cherry, Stacey
影响因子：
5.4
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通讯作者：
Schultz-Cherry, S
影响因子：
2.5
作者：
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通讯作者：
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影响因子：
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作者：
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