A 9-month-old boy who received routine BCG vaccination at birth presents with an enlarging ulcer at the vaccination site, axillary lymphadenopathy, and fever. Cultures grow Mycobacterium bovis BCG. Genetic testing reveals a loss-of-function mutation affecting the receptor for a cytokine produced by macrophages. The defective cytokine-receptor pair impairs production of which downstream cytokine?

• A Interleukin-10
• B Interleukin-4
• C Interferon-gamma ✓
• D Transforming growth factor-beta

Explanation

This is Mendelian susceptibility to mycobacterial disease caused by IL-12 receptor deficiency. Macrophage-derived IL-12 normally drives Th1 and NK cells to secrete interferon-gamma, which activates macrophage killing of intracellular mycobacteria; loss of signaling leaves the child unable to mount effective Th1 immunity against even attenuated BCG organisms. IL-4 and IL-10 are anti-inflammatory or Th2 cytokines and TGF-beta is immunosuppressive, none of which mediate mycobacterial killing.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.