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Published on: July 26, 2017
PPE65 of M. tuberculosis regulate pro-inflammatory signalling through LRR domains of Toll like receptor-2
Rahila Qureshi1, Nagender Rao Rameshwaram1, Madhu Babu Battu1
1Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Inner Ring Road, Uppal, Hyderabad, India.
Abstract:
Our understanding of the PE/PPE family of proteins in M. tuberculosis (Mtb) pathogenesis is still evolving and their critical roles in the host immunomodulation are still in the discovery process. Earlier studies from our group have shown that TLR2-LRR domain plays an important role in regulating cytokine signalling by PPE proteins. The importance of TLR2-LRR domain 16-20 in the regulation of PPE17-induced pro-inflammatory signalling has been established recently. However, it is yet to find whether other PPE protein also targets the TLR2-LRR 16-20 domain for induction of pro-inflammatory responses. In the current study, we have explored the structural parameters and possible role of PPE65 in generating pro-inflammatory signalling molecules mediated through IRAK3 downstream of TLR2-LRR domain 16-20. This study conceptualizes the functional characteristics of PPE65 in infection condition and might possibly provide valuable information in exploring this protein as an immunomodulator in Mtb infection.
Insights
The PE/PPE protein family in Mycobacterium tuberculosis (Mtb) is key to pathogenesis. This study investigates PPE65
Area of Science:
- Immunology
- Microbiology
- Structural Biology
Background:
- The PE/PPE protein family of Mycobacterium tuberculosis (Mtb) plays a crucial role in pathogenesis and host immune modulation.
- Previous research identified the Toll-like receptor 2 (TLR2) - Leucine-Rich Repeat (LRR) domain, specifically residues 16-20, as important for regulating cytokine signaling induced by PPE proteins, such as PPE17.
- It remains unclear if other PE/PPE proteins also target this specific TLR2-LRR domain (16-20) to induce pro-inflammatory responses.
Purpose of the Study:
- To explore the structural parameters of the PPE65 protein.
- To investigate the role of PPE65 in generating pro-inflammatory signaling molecules.
- To determine if PPE65 mediates its effects through IRAK3 downstream of the TLR2-LRR domain 16-20.
Main Methods:
- Structural analysis of PPE65.
- Investigating signaling pathways involving PPE65, TLR2-LRR domain 16-20, and IRAK3.
- Assessing the induction of pro-inflammatory molecules.
Main Results:
- The study explored the structural characteristics of PPE65.
- Evidence suggests PPE65 generates pro-inflammatory signaling molecules.
- The mechanism involves IRAK3 downstream of the TLR2-LRR domain 16-20.
Conclusions:
- PPE65 plays a role in generating pro-inflammatory signaling.
- This occurs via the TLR2-LRR domain 16-20 and IRAK3 pathway.
- PPE65 may serve as an immunomodulator in Mtb infections.
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