Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin.

Abstract

Bordetella pertussis filamentous hemagglutinin (FHA) is a surface-associated and secreted protein that serves as a crucial adherence factor, and displays immunomodulatory activity in human peripheral blood mononuclear cells (PBMCs). In order to appreciate more fully the role of secreted FHA in pathogenesis, we analyzed FHA-induced changes in genome-wide transcript abundance in human PBMCs. Among the 683 known unique genes with greater than 3-fold change in transcript abundance following FHA treatment, 125 (18.3%) were identified as interferon (IFN)-regulated. Among the latter group were genes encoding several members of the IFN type I response, as well as 3 key components of the ISGylation pathway. Using real-time RT-PCR, we confirmed FHA-associated increases in transcript abundance for the genes encoding ubiquitin-like protein, ISG15, and its specific protease USP18. Western-blot analysis demonstrated the presence of both, free ISG15 and several ISGylated conjugates in FHA-stimulated PBMC lysates, but not in unstimulated cells. Intracellular FACS analysis provided evidence that monocytes and a natural killer-enriched cell population were the primary producers of ISG15 in PBMCs after FHA stimulation. Our data reveal previously-unrecognized effects of B. pertussis FHA on host IFN and ISGylation responses, and suggest previously-unsuspected mechanisms by which FHA may alter the outcome of the host-pathogen interaction.

• Authors: Christine Dieterich, David A Relman
• Journal: PloS one (PLoS One) Vol. 6 Issue 11 Pg. e27535 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22140447 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adhesins, Bacterial
• Cytokines
• Inflammation Mediators
• Lipopolysaccharides
• RNA, Messenger
• Ubiquitins
• Virulence Factors, Bordetella
• filamentous hemagglutinin adhesin, Bordetella pertussis
• ISG15 protein, human
• Interferons

Topics

• Adhesins, Bacterial (isolation & purification, pharmacology)
• Bordetella pertussis (drug effects, metabolism)
• Cytokines (metabolism)
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Genome, Human (genetics)
• Host-Pathogen Interactions (drug effects)
• Humans
• Inflammation Mediators (metabolism)
• Interferons (immunology)
• Killer Cells, Natural (drug effects, metabolism)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Lipopolysaccharides (pharmacology)
• Monocytes (drug effects, metabolism)
• RNA, Messenger (genetics, metabolism)
• Signal Transduction (drug effects, immunology)
• Ubiquitins (immunology, metabolism)
• Virulence Factors, Bordetella (isolation & purification, pharmacology)