Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin.
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 patho...
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oai:doaj.org-article:a11cea804b764c9b98496a1764c7aba12021-11-18T07:33:24ZModulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin.1932-620310.1371/journal.pone.0027535https://doaj.org/article/a11cea804b764c9b98496a1764c7aba12011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22140447/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Bordetella 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.Christine DieterichDavid A RelmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27535 (2011) |
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Medicine R Science Q Christine Dieterich David A Relman Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin. |
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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. |
format |
article |
author |
Christine Dieterich David A Relman |
author_facet |
Christine Dieterich David A Relman |
author_sort |
Christine Dieterich |
title |
Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin. |
title_short |
Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin. |
title_full |
Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin. |
title_fullStr |
Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin. |
title_full_unstemmed |
Modulation of the host interferon response and ISGylation pathway by B. pertussis filamentous hemagglutinin. |
title_sort |
modulation of the host interferon response and isgylation pathway by b. pertussis filamentous hemagglutinin. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/a11cea804b764c9b98496a1764c7aba1 |
work_keys_str_mv |
AT christinedieterich modulationofthehostinterferonresponseandisgylationpathwaybybpertussisfilamentoushemagglutinin AT davidarelman modulationofthehostinterferonresponseandisgylationpathwaybybpertussisfilamentoushemagglutinin |
_version_ |
1718423304214151168 |