Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses.

Infection and Immunity
David J DowlingSandra M O'Neill

Abstract

Fasciola hepatica is a helminth pathogen that drives Th2/Treg immune responses in its mammalian host. The parasite releases a large number of molecules that are critical to inducing this type of immune response. Here we have selected recombinant forms of two major F. hepatica secreted molecules, the protease cathepsin L (rFhCL1) and an antioxidant, sigma class glutathione transferase (rFhGST-si), to examine their interactions with dendritic cells (DCs). Despite enzymatic and functional differences between these molecules, both induced interleukin-6 (IL-6), IL-12p40, and macrophage inflammatory protein 2 (MIP-2) secretion from DCs and enhanced CD40 expression. While this induction was mediated by Toll-like receptor 4 (TLR4), the subsequent intracellular signaling pathways differed; rFhCL1 signaled through p38, and rFhGST-si mediated its effect via c-Jun N-terminal kinase (JNK), p38, p-NF-kappaBp65, and IRF5. Neither rFhCL1 nor rFhGST-si enhanced DC phagocytosis or induced Th2 immune responses in vivo. However, DCs matured in the presence of either enzyme attenuated IL-17 production from OVA peptide-specific T cells in vivo. In addition, DCs exposed to either antigen secreted reduced levels of IL-23. Therefore, both F. hepatica F...Continue Reading

References

Jul 1, 1987·The American Journal of Tropical Medicine and Hygiene·A W CheeverK G Malley
Feb 1, 1995·Molecular and Biochemical Parasitology·L SalvatoreT W Spithill
Jan 1, 1995·European Journal of Immunology·S GillessenM K Gately
Sep 25, 1999·Infection and Immunity·M T BradyK H Mills
Feb 15, 2000·Parasite Immunology·S M O'NeillJ P Dalton
Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M WhelanK P Rigley
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J F ArrighiC Hauser
Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A S MacDonaldE J Pearce
Nov 6, 2002·The Journal of Biological Chemistry·Sudeepta AggarwalAustin L Gurney
May 3, 2003·Archives of Microbiology·James DeschnerSudha Agarwal
Dec 4, 2003·Nature Reviews. Immunology·Martien L Kapsenberg
Sep 14, 2004·Immunological Reviews·Rick M MaizelsJudith E Allen
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helen S GoodridgeMargaret M Harnett
Aug 6, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul G ThomasDonald A Harn
Sep 28, 2005·International Immunology·Stephen John JenkinsAdrian Paul Mountford
May 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anshu AgrawalBali Pulendran
Nov 28, 2006·Trends in Immunology·Andrea M Cooper, Shabaana A Khader
May 4, 2007·Inflammatory Bowel Diseases·Jonas Mudter, Markus F Neurath
Jan 16, 2008·The Journal of Experimental Medicine·Andrew S MacDonald, Rick M Maizels
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura I RutitzkyMiguel J Stadecker
Feb 13, 2008·Cell·Matthew S Hayden, Sankar Ghosh
May 29, 2008·Cellular Microbiology·Jacqueline G PerrigoueDavid Artis
Aug 19, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sheila DonnellyJohn P Dalton
Sep 11, 2008·Current Molecular Medicine·Ilse Gutierrez-Roelens, Bernard R Lauwerys
Jan 8, 2009·Immunology·Meredith M Curtis, Sing Sing Way

❮ Previous
Next ❯

Citations

Jun 6, 2012·PLoS Neglected Tropical Diseases·E James LaCoursePeter M Brophy
Nov 24, 2011·International Journal of Biological Sciences·César A TerrazasLorena Gómez-García
May 24, 2012·Nature Communications·Jen ClaridgeDiana J L Williams
Mar 24, 2011·Drug Metabolism Reviews·Jack U Flanagan, Mark L Smythe
Mar 8, 2013·Current Opinion in Immunology·Paola Zaccone, Anne Cooke
Nov 19, 2015·Parasite Immunology·Krisztina V VukmanSandra M O'Neill
Dec 12, 2012·International Journal for Parasitology·Mark W RobinsonSheila Donnelly
Dec 7, 2007·Trends in Parasitology·Paola ZacconeAnne Cooke
Jun 18, 2016·Parasite Immunology·K CwiklinskiJ P Dalton
Jul 2, 2014·The Lancet Infectious Diseases·Linda J WammesMaria Yazdanbakhsh
Apr 8, 2014·Molecular and Biochemical Parasitology·William Harnett
Apr 28, 2016·International Reviews of Immunology·Amin ZakeriAlireza Haghparast
Jun 18, 2015·Journal of the Neurological Sciences·Akhilesh SinghPraveen Kumar Sharma
Apr 14, 2011·FEBS Letters·Kristina Kakalacheva, Jan D Lünemann
Sep 17, 2014·Infection and Immunity·Olgary Figueroa-Santiago, Ana M Espino
Feb 26, 2011·Nature Reviews. Immunology·Polly Matzinger, Tirumalai Kamala
Nov 28, 2013·The Journal of Biological Chemistry·Victoria Martínez-SernándezFlorencio M Ubeira

❮ Previous
Next ❯

Related Concepts

Related Feeds