School of Medicine Publications
Document Type
Article
Publication Date
12-23-2025
Abstract
Perspectives beyond the CD4 T cell interferon (IFN)-γ paradigm are needed to understand immunity in tuberculosis (TB). Growing data in patients across a spectrum of TB highlight that changes in antibody Fc domain glycosylation and Fc effector functions correlate with disease and impact Mycobacterium tuberculosis (Mtb) infection. How antigen-specific antibodies within polyclonal responses affect bacteria is less clear. This study examines antibodies targeting ESAT-6 and CFP-10, Mtb virulence proteins essential for pathogenesis. Data from patients with TB show that polyclonal immunoglobulin (Ig)G reactive to ESAT-6 and CFP-10 diverges from other Mtb and non-Mtb antigens with enhanced sialylation, afucosylation, natural killer cell-mediated cellular cytotoxicity, and association with anti-microbial activity against intracellular Mtb. Monoclonal antibody studies show that intracellular Mtb inhibition is dependent on antigen binding, N-linked glycans, and Fc-Fc receptor (FcR) engagement. These findings demonstrate that some antibodies in patients inhibit Mtb in its quintessential intracellular niche, opening avenues to appreciate how humoral immunity impacts TB.
Recommended Citation
Miles, J. R., Lu, P., Bai, S., Aguillón-Durán, G. P., Rodríguez-Herrera, J. E., Gunn, B. M., ... & Lu, L. L. (2025). ESAT-6 and CFP-10 reactive IgG in patients with tuberculosis inhibits intracellular bacteria. Cell Reports, 44(12). https://doi.org/10.1016/j.celrep.2025.116653
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Publication Title
Cell Reports
DOI
10.1016/j.celrep.2025.116653
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
http://creativecommons.org/licenses/by-nc/4.0/