Pathology · Inflammation (Acute, Chronic, Granulomatous, Mediators)

In granulomatous inflammation caused by Mycobacterium tuberculosis, which innate pattern recognition receptor (PRR) pathway is primarily responsible for recognizing mycobacterial components and initiating the granuloma-forming Th1 response?

  • A TLR2 recognition of mycobacterial lipoarabinomannan (LAM) and lipoproteins on macrophages, signalling through MyD88 to activate NF-κB and produce IL-12 for Th1 polarization
  • B NOD2 recognition of mycobacterial MDP (muramyl dipeptide) activating RIPK2-NF-κB axis exclusively
  • C RIG-I recognition of mycobacterial RNA activating STING-IRF3 pathway to produce type I interferons as the primary granuloma-inducing signal
  • D NLRP3 inflammasome activation by mycobacterial cholesterol as the primary driver of granuloma formation via IL-1β
Correct answer: A. TLR2 recognition of mycobacterial lipoarabinomannan (LAM) and lipoproteins on macrophages, signalling through MyD88 to activate NF-κB and produce IL-12 for Th1 polarization

Explanation

TLR2 (and also TLR4, TLR9) on macrophages recognize mycobacterial pathogen-associated molecular patterns (PAMPs) — particularly TLR2 recognizes lipoarabinomannan (LAM), lipomannan (LM), and mycobacterial lipoproteins. TLR signalling via MyD88 activates NF-κB, inducing pro-inflammatory cytokines including TNF-α and crucially IL-12. IL-12 drives naive T-cell differentiation toward Th1 phenotype (IFN-γ producing), which activates macrophages for mycobacterial killing and granuloma maintenance. IFN-γ from Th1 cells, together with TNF-α, maintains the granuloma architecture. NOD2 recognizes MDP and contributes but is not the primary initiator. RIG-I senses viral RNA. NLRP3 inflammasome contributes to pathology but is not the primary granuloma-initiating pathway.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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