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J Leukoc Biol. 2012 Jul;92(1):11-20. doi: 10.1189/jlb.0911479. Epub 2012 Mar 21.

Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages.

Author information

1
Institute of Immunology, University of Muenster, Muenster, Germany.

Abstract

Systemic infections with HPAIVs, such as H5N1, are characterized by cytokine burst and sepsis. We investigated the role of human monocyte-derived macrophages in these events after infection with different influenza virus strains. Macrophages were infected with low pathogenic H1N1 (PR8) or high pathogenic H7N7 (FPV) and H5N1 (KAN-1) subtypes. Macrophages were found to be nonpermissive for influenza virus propagation. Surprisingly, transcriptome analysis revealed an insufficient innate immune response of macrophages only to HPAIV infections. Induction of inflammatory cytokines, as well as type I IFNs, was significantly attenuated in H5N1- and H7N7-infected cells, contradicting a primary role of macrophages for the cytokine burst. Furthermore, inflammasome activation was impaired significantly in HPAIV-infected macrophages. Interestingly, this finding correlated with a complete suppression of viral protein M2 expression after HPAIV infection, which is known to be involved in influenza viral inflammasome activation. In summary, our data provide first evidences for a strategy of how HPAIVs avoid initial inflammatory responses of macrophages facilitating virus spreading and progression to the systemic stage of disease.

PMID:
22442495
PMCID:
PMC3382316
DOI:
10.1189/jlb.0911479
[Indexed for MEDLINE]
Free PMC Article

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