Subverting bradykinin-evoked inflammation by co-opting the contact system: lessons from survival strategies of Trypanosoma cruzi

Current Opinion in Hematology
Julio Scharfstein

Abstract

During Chagas disease, Trypanosoma cruzi alternates between intracellular and extracellular developmental forms. After presenting an overview about the roles of the contact system in immunity, I will review experimental studies showing that activation of the kallikrein-kinin system (KKS) translates into mutual benefits to the host/parasite relationship. T. cruzi trypomastigotes initiate inflammation by activating tissue-resident innate sentinel cells via the TLR2/CXCR2 pathway. Following neutrophil-evoked microvascular leakage, the parasite's major cysteine protease (cruzipain) cleaves plasma-borne kininogens and complement C5. Tightly regulated by angiotensin-converting enzyme (ACE), kinins and C5a in turn further propagate inflammation via iterative cycles of mast cell degranulation, contact system activation, bradykinin release and activation of endothelial bradykinin B2 receptors (B2R). Recently, studies in the intracardiac model of infection revealed a dichotomic role for bradykinin and endothelin-1: generated upon contact activation (mast cell/KKS pathway), these pro-oedematogenic peptides reciprocally stimulate trypomastigote invasion of heart cells that naturally overexpress B2R and endothelin receptors (ETaR/ETbR). Stu...Continue Reading

References

Sep 2, 1991·Science·D Gailani, G J Broze
Nov 5, 1997·The Journal of Biological Chemistry·E Del NeryL Juliano
Nov 9, 2000·The Journal of Experimental Medicine·J ScharfsteinW Müller-Esterl
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·M A CamposR T Gazzinelli
Dec 1, 2001·The Journal of Biological Chemistry·Ana Paula C A LimaJulio Scharfstein
Nov 9, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alex G TodorovJulio Scharfstein
Dec 20, 2002·International Immunopharmacology·Zia Shariat-MadarAlvin H Schmaier
May 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julio AlibertiJulio Scharfstein
Mar 24, 2005·Infection and Immunity·Herbert B TanowitzMasashi Yanagisawa
Jul 13, 2005·The Journal of Experimental Medicine·Thomas RennéBernhard Nieswandt
Sep 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andre BaficaAlan Sher
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana Carolina MonteiroJulio Scharfstein
Nov 10, 2006·The EMBO Journal·Inga-Maria FrickLars Björck
Sep 11, 2008·Annals of Tropical Medicine and Parasitology·L A BenvenutiM L Higuchi
Sep 24, 2008·Medical Microbiology and Immunology·Wendy E KamanDesiree van der Kleij
Nov 26, 2008·Microbes and Infection·Ana Claudia Trocoli TorrecilhasMaria Júlia Manso Alves
Aug 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana Carolina MonteiroJulio Scharfstein
Jan 1, 2009·Journal of Innate Immunity·Sonja OehmckeHeiko Herwald
Aug 3, 2010·Nature Medicine·Steffen MassbergBernd Engelmann
Sep 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Umme AmaraMarkus Huber-Lang
Mar 16, 2011·Infection and Immunity·Anne-Danielle C ChesslerBarbara A Burleigh
Sep 3, 2011·Advances in Parasitology·Cibele M PradoMarcos A Rossi
Feb 9, 2012·Cellular Microbiology·Fnu NagajyothiHerbert B Tanowitz
Mar 28, 2012·The Journal of Experimental Medicine·Marie-Luise von BrühlSteffen Massberg
Jun 26, 2012·The Journal of Clinical Investigation·Claudia N PaivaMarcelo T Bozza
Jul 5, 2012·The Journal of Biological Chemistry·David Moreno-SanchezRoberto Docampo
Nov 16, 2012·Parasites & Vectors·Dirlei NicoClarisa Beatriz Palatnik-de-Sousa
Dec 12, 2012·Nature Reviews. Immunology·Bernd Engelmann, Steffen Massberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.