High-throughput analysis of T cell-monocyte interaction in human tuberculosis.

Area of Science:

• Immunology
• Infectious Diseases
• Cellular Biology

Background:

• Developing effective tuberculosis (TB) control strategies requires understanding host immune responses.
• Existing tools for identifying immunological correlates of TB protection or disease progression are insufficient.
• Previous work established an imaging flow cytometry (IFC) assay for T cell-monocyte interactions.

Purpose of the Study:

• To characterize T cell-monocyte communication in individuals with varying TB infection statuses.
• To utilize clinical samples from a TB-endemic region to validate the IFC assay.
• To identify potential immunological markers for TB protection and disease progression.

Main Methods:

• Peripheral blood mononuclear cells (PBMC) from TB patients, latent TB-infected (LTBI) individuals, and healthy controls were stimulated.
• Stimulation involved Mycobacterium bovis bacille Calmette-Guérin (BCG) or early secreted antigenic target 6 (ESAT-6) peptides.
• Cells were analyzed using IFC, assessing T cell-monocyte conjugates, T cell receptor (TCR) polarization, F-actin, and nuclear factor kappa B (NF-κB) translocation.

Main Results:

• A reduced frequency of T cell-monocyte conjugates was observed in active pulmonary TB (pTB) patients compared to LTBI and healthy controls.
• A significantly higher proportion of T cells showed NF-κB nuclear translocation when interacting with monocytes in active pTB patients.
• These findings highlight distinct T cell-monocyte communication patterns across different TB infection states.

Conclusions:

• IFC is a valuable tool for assessing complex host immune responses in TB.
• Multiple immunological parameters should be considered for a comprehensive understanding of TB.
• The study provides insights into host-pathogen interactions relevant to TB pathogenesis and control.