Monocyte response receptors in BCG driven delayed type hypersensitivity to tuberculin

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Tuberculosis (TB) remains a major global health threat, with the Bacille Calmette-Guérin (BCG) vaccine offering variable protection.
• Delayed type hypersensitivity (DTH) to tuberculin, detected via purified protein derivative (PPD) skin testing, is a measure of BCG-induced cell-mediated immunity.
• Previous studies suggest a link between CD14 gene polymorphism and DTH response to PPD in BCG-vaccinated individuals.

Purpose of the Study:

• To investigate the role of CD14 in the BCG-driven DTH response to PPD.
• To examine the expression of CD14 on macrophages and serum levels of soluble CD14 (sCD14).
• To determine the association between polymorphisms in Toll-like receptor (TLR) genes (TLR2 and TLR4) and DTH skin reactivity to PPD.

Main Methods:

• Measurement of monocyte and macrophage CD14 expression (mCD14) in BCG-vaccinated volunteers with and without PPD skin reactivity.
• Quantification of serum sCD14 levels.
• Genotyping of CD14, TLR2, and TLR4 gene polymorphisms.
• Assessment of TLR2 expression on monocytes.

Main Results:

• A subtle but significant decrease in CD14 density was observed on adherent monocytes from tuberculin-positive compared to tuberculin-negative volunteers.
• CD14 density increased on macrophages stimulated with PPD and LPS, but not live BCG, with similar increases and sCD14 levels in both PPD-reactive groups.
• No association was found between CD14, TLR2, or TLR4 gene polymorphisms and PPD skin responses, nor differences in TLR2 density on monocytes.

Conclusions:

• The role of CD14 in generating DTH to tuberculin in BCG-vaccinated subjects warrants further investigation.
• CD14 gene variants may influence DTH development, but the observed differences in monocyte CD14 density were subtle.
• TLR gene polymorphisms and TLR2 expression did not appear to be associated with PPD skin reactivity in this cohort.