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
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.
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
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
19.
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
21.
22. INVOLVES 2 TYPES OF REGULATORYINVOLVES 2 TYPES OF REGULATORY
CASCADES:CASCADES:
TRANSCRIPTION FACTOR ACTIVATIONTRANSCRIPTION FACTOR ACTIVATION
CHROMATIN MODIFICATIONCHROMATIN MODIFICATION
23.
24.
25.
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.
Editor's Notes
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.
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