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Original scientific paper

Pathogenic Hantaviruses Elicit Different Immunoreactions in THP-1 Cells and Primary Monocytes and Induce Differentiation of Human Monocytes to Dendritic-Like Cells

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

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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 -chemokines and their receptors. In contrast, THP-1 cells, expressed receptors
for CXC chemokines. Surprisingly, infected macrophages underwent morphological changes toward dendriticlike
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.


pathogenic hantaviruses; THP-1 cells; primary monocytes; dendritic-like cells; cytokines/chemokines

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