dysregulation of macrophage signal transduction by toxoplasma
TRANSCRIPT
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Discovered in 1908 in desert rodent Ctenodactylus gundi, in a colony maintained at the Pasteur institute in Tunis by Nicolle and Manceaux
3 strains : I, II, IIIBased on pathogenicity in miceType I highly pathogenic no cyst formationType II and III less pathogenic , cyst formationStrains differ in terms of the immune responses
they elicit.
Evasion Robust immune response
.
As intracellular parasite Toxoplasma gondii lives inside macrophages
Not only survives in macrophages but also multiplies
Copes up with panel of antimicrobial host mechanisms
Done by dysregulation of signal transduction in macrophages
Effector Molecules: Rhoptries proteins
Parasite ImmunologyVolume 31,
NEUTRALIZATION OF IFN-γ INDUCED RESPONSES….IFN-γ Receptor signalling is also under feedback of
SOCS-1Toxoplasma gondii has been shown to induce
SOCS-1SOCS binds tyrosine phosphorylated JAK
(The Journal of Immunology, 2006, 176: 1840–1847.)
IL- 10, an anti-inflammatory Th2 cytokine.T gondii affects host macrophages much like IL-10bypasses IL-10 and directly activates anti-inflammatory
signaling.ROP16 targets host signal transduction machinery—
JAK/STAT signaling
T gondii down regulates proinflammatory cytokinesIL-12 and TNF-α synthesis inhibitedDone by inhibition of TLR signallingThrough NFkB and MAPK pathwaysGeneral phenomenon and not strain restricted
INVOLVES 2 TYPES OF REGULATORY INVOLVES 2 TYPES OF REGULATORY CASCADES:CASCADES:
TRANSCRIPTION FACTOR ACTIVATIONTRANSCRIPTION FACTOR ACTIVATION
CHROMATIN MODIFICATIONCHROMATIN MODIFICATION
Dysregulation of macrophage signal transduction by Toxoplasma gondii: past progress and recent advances J. LENG, B. A. BUTCHER & E. Y. DENKERS Parasite Immunology, 2009, 31, 717–728
Toxoplasma Rhoptries: Unique Secretory Organelles and Source of Promising Vaccine Proteins for Immunoprevention of Toxoplasmosis Henryka Dlugonska Journal of Biomedicine and Biotechnology Volume 2008 (2008), Article ID 632424, 7 pages
Toxoplasma gondii Parasites Take Control within Host Cells Eric Y. Denkers and Barbara A. Butcher Microbe—Volume 7, Number 8, 2012Toxoplasma gondii Inhibits Gamma Interferon (IFN-γ)- and IFN-β-Induced Host Cell STAT1 Transcriptional Activity by Increasing the Association of STAT1 with DNA Infect Immun. Feb 2014; 82706–719 Emily E. Rosowski, Quynh P. Nguyen,Ana Camejo, Eric Spooner, and Jeroen P. J. Saei
Toxoplasmosis of humans and animals ; Second edition J.P Dubey Induction of Suppressor of Cytokine Signaling-1 by Toxoplasma gondii Contributes
to Immune Evasion in Macrophages by Blocking IFN-γ Signaling Stefan Zimmermann,* Peter J. Murray,† Klaus Heeg, and Alexander H. Dalpke The Journal of Immunology, 2006, 176: 1840–1847.
