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致病性汉坦病毒在THP-1细胞和原代单核细胞中引发不同的免疫反应,并诱导人单核细胞分化为树突状样细胞。

Pathogenic hantaviruses elicit different immunoreactions in THP-1 cells and primary monocytes and induce differentiation of human monocytes to dendritic-like cells.

作者信息

Markotić Alemka, Hensley Lisa, Daddario Kathleen, Spik Kristin, Anderson Kevin, Schmaljohn Connie

机构信息

Scientific Unit, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", Zagreb, Croatia.

出版信息

Coll Antropol. 2007 Dec;31(4):1159-67.

Abstract

Hantaviruses cause two important human illnesses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Both syndromes are believed to be immune-mediated diseases. Monocytes/macrophages are thought to be the main target cells for hantaviruses and important sources of and targets for cytokines/chemokines secretion. THP-1 cells have been used extensively as models for primary monocytes in biocompatibility research. The aim of our study was to determine if hantaviruses induce the same immunoreactions in THP-1 cells and primary monocytes/ macrophages and might therefore be suitable for immune studies of hantaviral infections. For that purpose we compared various cytokines/chemokines and their receptors in THP-1 cell line and primary monocytes/macrophages. Infected primary monocytes/macrophages induced mostly beta-chemokines and their receptors. In contrast, THP-1 cells, expressed receptors for CXC chemokines. Surprisingly, infected macrophages underwent morphological changes toward dendritic-like cells and increased expression of co-stimulatory molecules: CD40, CD80, CD83 and CD86. Our data indicate that THP-1 cells are not ideal for in vitro research of the immunopathogenesis of hantaviruses in humans. Further, our studies revealed potential roles for cytokines/chemokines in HFRS/HPS immunopathogenesis and point to intriguing possibilities for the possible differentiation of infected macrophages to dendritic-like cells.

摘要

汉坦病毒可引发两种重要的人类疾病,即肾综合征出血热(HFRS)和汉坦病毒肺综合征(HPS)。这两种综合征均被认为是免疫介导性疾病。单核细胞/巨噬细胞被认为是汉坦病毒的主要靶细胞,也是细胞因子/趋化因子分泌的重要来源和靶标。在生物相容性研究中,THP - 1细胞已被广泛用作原代单核细胞的模型。我们研究的目的是确定汉坦病毒在THP - 1细胞和原代单核细胞/巨噬细胞中是否诱导相同的免疫反应,因此是否适合用于汉坦病毒感染的免疫研究。为此,我们比较了THP - 1细胞系和原代单核细胞/巨噬细胞中各种细胞因子/趋化因子及其受体。受感染的原代单核细胞/巨噬细胞主要诱导β - 趋化因子及其受体。相比之下,THP - 1细胞表达CXC趋化因子的受体。令人惊讶的是,受感染的巨噬细胞向树突状细胞发生形态变化,并增加共刺激分子CD40、CD80、CD83和CD86的表达。我们的数据表明,THP - 1细胞并非人类汉坦病毒免疫发病机制体外研究的理想模型。此外,我们的研究揭示了细胞因子/趋化因子在HFRS/HPS免疫发病机制中的潜在作用,并指出受感染巨噬细胞可能分化为树突状细胞的有趣可能性。

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