Naslov
The possible role of cytokines, chemokines and their receptors in the immunopathogenesis of HFRS and HPS

Autori
Markotić, Alemka ; Anderson, Kevin ; Schmaljohn, Connie

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract Book / - , 2001, 103-103

Skup
The Fifth International Conference on HFRS, HPS and Hantaviruses

Mjesto i datum
Veyrier-du-Lac, Francuska, 13.06.2001. - 16.06.2001

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Sažetak
Objectives: Hantaviruses cause two severe human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Several studies support the view that immunological responses to hantavirus infection contribute to the pathogenesis of HFRS and HPS. To investigate the possible role of cytokines, chemokines and their receptors in HFRS and HPS immunopathogenesis we compared their induction in human cell lines infected with the HFRS-causing hantavirus, Hantaan virus (HTNV) or with the HPS-causing hantaviruses, Sin Nombre (SNV) or Andes (ANDV) viruses. Methods: We infected THP-1 (a human monocyte line), primary human monocytes, 293HEK (human epithelial kidney line), MRC-5 (fetal lung fibroblasts cell line), and human vein endothelial cells (HUVEC) with HTNV, SNV or ANDV. Culture supernatants were assayed by ELISA for the presence of cytokines (IL-1beta, IL-6, IL-10, IL-12 p40, TNF-alpha, IFN-gamma) and CC and CXC chemokines (RANTES, MIP-1alpha, MIP-1beta, MCP-1, IL-8). To measure induction of cytokine and CC and CXC chemokine receptors, we extracted total cellular RNA from virus-infected cells at selected times after infection and used RiboQuant^TM multi-probe RNase protection assays. Results: We observed that, following infection, HFRS and HPS viruses induced different cytokine and chemokine patterns in tested cells. Namely, HTNV induced GM-CSF in MRC-5 cell line and RANTES in 293HEK, while HPS viruses induced some TNF-alpha in THP-1 cells and HUVEC and MCP-1 in 293HEK, respectively. Interestingly, HPS-causing hantaviruses induced IL-10 secretion in 293HEK cell line which might explain the lack of kidney inflammation in infected individuals. Another hallmark of HTNV infection was induction of CCR4 mRNA expression in 293HEK cells, one of the RANTES receptors. HTNV also induced both RANTES secretion and increased mRNA expression of its receptors, CCR1 and CCR5, in infected primary human monocytes, which might contribute in both autocrine and paracrine manner to the homing and enrolment of these cells during infection in target organs. Conclusion: The complex network of cytokines, chemokines and their receptors may have a role in HFRS and HPS. Further in vitro and clinical studies are necessary to determine if the differences that we noted in cells infected with HFRS or HPS hantaviruses have bearing on the differing immunopathogenesis of HFRS and HPS in humans.

Izvorni jezik
Engleski

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