Hyper-responsive Toll-like receptor 7 and 9 activation in NADPH oxidase-deficient B lymphoblasts

Immunology
Shawna McLetchieJanice S Blum

Abstract

Chronic granulomatous disease (CGD) is an inherited immunodeficiency linked with mutations in the multi-subunit leucocyte NADPH oxidase. Myeloid-derived phagocytic cells deficient in NADPH oxidase fail to produce sufficient levels of reactive oxygen species to clear engulfed pathogens. In this study we show that oxidase also influences B-cell functions, including responses to single-stranded RNA or unmethylated DNA by endosomal Toll-like receptors (TLRs) 7 and 9. In response to TLR7/9 ligands, B-cell lines derived from patients with CGD with mutations in either the NADPH oxidase p40(phox) or p47(phox) subunits produced only low levels of reactive oxygen species. Remarkably, cytokine secretion and p38 mitogen-activated protein kinase activation by these oxidase-deficient B cells was significantly increased upon TLR7/9 activation when compared with oxidase-sufficient B cells. Increased TLR responsiveness was also detected in B cells from oxidase-deficient mice. NADPH oxidase-deficient patient-derived B cells also expressed enhanced levels of TLR7 and TLR9 mRNA and protein compared with the same cells reconstituted to restore oxidase activity. These data demonstrate that the loss of oxidase function associated with CGD can signifi...Continue Reading

References

Aug 21, 2002·Genome Biology·Myriam A Armant, Matthew J Fenton
Sep 30, 2003·Scandinavian Journal of Infectious Diseases·Adilia WarrisTore G Abrahamsen
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Scott D KobayashiFrank R DeLeo
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Malin HultqvistRikard Holmdahl
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marisa VulcanoSilvano Sozzani
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Silvia BellocchioLuigina Romani
Aug 19, 2005·Advances in Experimental Medicine and Biology·Johan BylundDavid P Speert
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·F Stephen LarouxCox Terhorst
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jack J BleesingThomas A Fleisher
Oct 3, 2006·Current Opinion in Immunology·Virginia PascualJacques Banchereau
Oct 26, 2006·Nature Reviews. Immunology·Ann Marshak-Rothstein
Jul 5, 2007·Journal of Virology·Heather J MartinS Diane Hayward
Jan 15, 2008·Journal of Clinical Immunology·S D Rosenzweig
Apr 3, 2008·European Journal of Immunology·Annie George-ChandyKristina Eriksson
Aug 5, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Kelly L BrownDavid P Speert
Aug 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jayakumar S PoovasseryGail A Bishop
Oct 31, 2009·European Journal of Immunology·Sabrina M Richards, Edward A Clark
Jan 14, 2010·Immunology·Isabelle Bekeredjian-Ding, Gaetan Jego
Apr 7, 2010·Antioxidants & Redox Signaling·Roberta VenéAnna Rubartelli
Aug 3, 2011·Clinical & Developmental Immunology·Nikolaus RieberDominik Hartl
Aug 31, 2011·Enzyme Research·Daniel J Loegering, Michelle R Lennartz
Mar 22, 2012·Immunologic Research·T CelharA-M Fairhurst
Sep 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victoria L CrotzerJanice S Blum
Oct 2, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew L Wheeler, Anthony L Defranco
Oct 27, 2012·Science Translational Medicine·Allison M CampbellMark J Shlomchik
Dec 13, 2012·Annals of the New York Academy of Sciences·Michael K MansourJatin M Vyas
Jun 19, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Kabir MatharuJohn I Gallin
Aug 3, 2013·Frontiers in Cellular and Infection Microbiology·Eva Brencicova, Sandra S Diebold
Sep 27, 2013·Frontiers in Immunology·Gail J GardinerJanice S Blum
Oct 1, 2013·Journal of Clinical Immunology·A C BattersbyA R Gennery
Jan 1, 2014·Methods in Enzymology·A Paige Davis Volk, Jessica G Moreland
Mar 12, 2015·Clinical Science·Julien CachatKarl-Heinz Krause
Mar 31, 2015·Journal of Leukocyte Biology·István KovácsMiklós Geiszt

❮ Previous
Next ❯

Citations

Jul 16, 2019·Current Opinion in Immunology·William M Nauseef
Jun 22, 2021·Frontiers in Immunology·Alexia Dumas, Ulla G Knaus

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.