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.

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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