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Published ahead of print on November 11, 2005, doi:10.1165/rcmb.2005-0287OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 3, March 2006, 320-329

A more recent version of this article appeared on March 1, 2006
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Submitted on July 25, 2005
Revised on November 11, 2005

Differential Response of Dendritic Cells to Human Metapneumovirus and Respiratory Syncytial Virus

Antonieta Guerrero-Plata1, Antonella Casola2, Giovanni Suarez1, Xiang Yu1, LeAnne Spetch1, Mark E Peeples3, and Roberto P Garofalo2*

1 Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA, 2 Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA, 3 Department of Pediatrics, Ohio State University, Columbus, OH, USA

* To whom correspondence should be addressed. E-mail: rpgarofa{at}utmb.edu.

Dendritic cells (DCs) play a pivotal role in shaping antiviral immune responses in the respiratory tract. Human metapneumovirus (hMPV) is a recently identified pathogen and like its better known relative, respiratory syncytial virus (RSV), has been increasingly recognized as a major cause of respiratory morbidity in infants and elderly. In the present study, we examined susceptibility as well as cellular responses of human DCs to hMPV compared to RSV. Monocyte-derived DCs (moDCs) were susceptible to infection by both viruses, but only RSV was able to induce a productive infection with release of viral progeny. Despite the fact that viral infection resulted in phenotypic maturation of moDCs, as shown by the upregulation of cell surface markers and antigen presenting molecules (MHC I and II, CD80, CD83, CD86, CD38), RSV-infected moDCs showed a severely impaired capacity to stimulate CD4+ T cell proliferation. Compared to hMPV, RSV was a more potent inducer of inflammatory and immunomodulatory cytokines, including TNF-{alpha}, IL-6, IL-1{beta}, IL-10, and IL-12p70 in both moDCs and plasmacytoid dendritic cells (pDCs). On the other hand, hMPV, but not RSV, was able to trigger production of interferon alpha (IFN-{alpha}) by moDCs, while both viruses strongly induced IFN-{alpha} in pDCs. Finally, both viruses strikingly suppressed INF-{alpha} production by moDCs or pDCs stimulated with synthetic dsRNA and CpG-ODN, respectively. The findings provide novel evidence that RSV and hMPV differentially activate human DCs and may use distinct mechanisms to interfere with the host innate and adaptive immune responses.




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