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Pediatr Res. 2010 Apr;67(4):345-51. doi: 10.1203/PDR.0b013e3181d22a73.

Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis by Mip2/Cxcl2.

Author information

1
Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.

Abstract

Biliary atresia is an obstructive cholangiopathy of unknown etiology. Although the adaptive immune system has been shown to regulate the obstruction of bile ducts in a rotavirus-induced mouse model, little is known about the virus-induced inflammatory response. Here, we hypothesized that cholangiocytes secrete chemoattractants in response to rotavirus. To test this hypothesis, we infected cholangiocyte and macrophage cell lines with rhesus rotavirus type A (RRV), quantified cytokines and chemokines and measured the migration of splenocytes. We also used PCR and immunostaining to search for new cellular targets of RRV in the liver. We found that RRV-infected cholangiocytes induced the mRNA expression for chemokines, but conditioned media failed to promote chemotaxis of splenocytes. Analyzing livers after viral challenge, we detected RRV in hepatic macrophages and demonstrated that media from RRV-infected macrophages have high concentrations of cytokines and chemokines and induced chemotaxis of neutrophils. Most notably, addition of anti-Mip2/Cxcl2 antibodies depleted this chemokine in the conditioned media and completely prevented neutrophil chemotaxis. In conclusion, infected cholangiocytes did not promote chemotaxis of inflammatory cells. Investigating alternate cellular targets of RRV, we detected the virus in hepatic macrophages and found that infected macrophages promoted neutrophil chemotaxis by release of Mip2/Cxcl2 in response to RRV.

PMID:
20234283
PMCID:
PMC2936668
DOI:
10.1203/PDR.0b013e3181d22a73
[Indexed for MEDLINE]
Free PMC Article

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