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© Research
Publication : European journal of immunology

Cytotoxicity and interleukin-1beta processing following Shigella flexneri infection of human monocyte-derived dendritic cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in European journal of immunology - 01 May 2002

Edgeworth JD, Spencer J, Phalipon A, Griffin GE, Sansonetti PJ

Link to Pubmed [PMID] – 11981835

Eur. J. Immunol. 2002 May;32(5):1464-71

Shigella flexneri infection of macrophages (MPhi) leads to activation of caspase-1 by the IpaB virulence factor, which induces rapid cell death and release of mature IL-1beta. Here we show that S. flexneri infection of human monocyte-derived dendritic cells (DC) also results in rapid IpaB-dependent death. Cytotoxicity is only partially blocked by the caspase-1 inhibitor YVAD, but completely blocked by the pan-caspase inhibitor z-VAD. Cytotoxicity is also partially blocked by glycine without affecting caspase-1-dependent IL-1beta processing, and treatment with glycine and YVAD completely blocks cytotoxicity, implying that glycine inhibits a caspase-1-independent cytotoxic mechanism. S. flexneri infection of LPS-pre-treated DC and Mphi results in comparable release of mature IL-1beta, although DC release significantly less IL-18 than MPhi. IL-1beta release from infected DC occurs within 3 h of the initial LPS pre-stimulation signal, implying that infection of DC will contribute towards induction of the early inflammatory response. The rapid death of DC during the early stages of shigellosis is likely to have adverse consequences for generation of adaptive immunity.

http://www.ncbi.nlm.nih.gov/pubmed/11981835