Dysregulation of macrophage signal transduction by Toxoplasma
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A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
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Dysregulation of macrophage signal transduction by Toxoplasma
- 3. Discovered in 1908 in desert rodent Ctenodactylus gundi, in a colony maintained at the Pasteur institute in Tunis by Nicolle and Manceaux
- 5. Clin Microbiol Rev. Apr 1998; 11(2): 267–299.
- 8. 3 strains : I, II, III Based on pathogenicity in mice Type I highly pathogenic no cyst formation Type II and III less pathogenic , cyst formation Strains differ in terms of the immune responses they elicit.
- 9. Evasion Robust immune response
- 12. . 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
- 14. Effector Molecules: Rhoptries proteins
- 17. NEUTRALIZATION OF IFN-γ INDUCED RESPONSES…. IFN-γ Receptor signalling is also under feedback of SOCS-1 Toxoplasma gondii has been shown to induce SOCS-1 SOCS binds tyrosine phosphorylated JAK (The Journal of Immunology, 2006, 176: 1840– 1847.)
- 18. IL- 10, an anti-inflammatory Th2 cytokine. T gondii affects host macrophages much like IL-10 bypasses IL-10 and directly activates anti-inflammatory signaling. ROP16 targets host signal transduction machinery— JAK/STAT signaling
- 20. T gondii down regulates proinflammatory cytokines IL-12 and TNF-α synthesis inhibited Done by inhibition of TLR signalling Through NFkB and MAPK pathways General phenomenon and not strain restricted
- 22. INVOLVES 2 TYPES OF REGULATORYINVOLVES 2 TYPES OF REGULATORY CASCADES:CASCADES: TRANSCRIPTION FACTOR ACTIVATIONTRANSCRIPTION FACTOR ACTIVATION CHROMATIN MODIFICATIONCHROMATIN MODIFICATION
- 26. 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.
Notas del editor
- The toll‐like receptor signalling cascade: impact of Toxoplasma infection. In a generalized pathway, TLR binding to its ligand (step 1) results in recruitment of the MyD88 adaptor molecule (step 2). In turn, this mediates recruitment of IL‐1 receptor‐associated kinase (IRAK) 1 and IRAK4, which form a complex with TRAF6 (step 3). In step 4, the TRAF6 molecule interacts with Uva1 and Ubc13, triggering ubiquitination of TRAF6. This stimulates activation of TAK1 which is associated with TAK1‐binding proteins (TAB) 1 and TAB2 (step 5). Activated TAK1 possesses MAPK kinase kinase activity, triggering MAPK activation (step 6). The TAK1 molecule also activates the IKK complex (step 7) leading in turn to degradation of IκBα and nuclear translocation of NFκB p50 : p65. Toxplasma blocks most, but not all TLR‐induced cytokine responses. There is evidence that the parasite blocks nuclear NFκB translocation, although this is a temporary effect. There are also data to suggest that the parasite interferes with TLR‐induced MAPK activation. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.