Markotić Alemka, Hensley Lisa, Daddario Kathleen, Spik Kristin, Anderson Kevin, Schmaljohn Connie
Scientific Unit, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", Zagreb, Croatia.
Coll Antropol. 2007 Dec;31(4):1159-67.
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.
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。