P-1374. Immunological Evaluation of Individuals with Multidrug-Resistant Tuberculosis in Callao, Peru

TL;DR

This study compares immune responses in people with drug-resistant and drug-sensitive tuberculosis in Peru, finding differences in T cells and IL-17 production.

Contribution

The study identifies distinct immune signatures in MDR-TB patients, including increased IL-17 and altered CD8+ T cell profiles.

Findings

CD8+ T cells were increased in MDR-TB patients compared to DS-TB patients.

MDR-TB patients showed decreased CD8+/CD38+ T cells compared to DS-TB patients.

IL-17 production was higher in MDR-TB patients when stimulated with Mtb antigens.

Abstract

Mycobacterium tuberculosis (Mtb) causes significant morbidity and mortality with worse outcomes in individuals infected with multi-drug resistant Mtb (MDR-TB). Specific MDR-TB strains have shown additional virulence factors that could prompt altered host immune response in comparison to drug susceptible Mtb (DS-TB). We evaluated the immune response of individuals with MDR-TB in Callao, Peru compared to DS-TB.Mtb-specific IL-17 production from PBMC collected from participants newly diagnosed with MDR-TB and DS-TB.Boxes show mean, min, and max values of fold change in IL-17 between ESAT-6·CFP-10-stimulated vs. unstimulated conditions. *p < 0.05

Mtb-specific IL-17 production from PBMC collected from participants newly diagnosed with MDR-TB and DS-TB.

Boxes show mean, min, and max values of fold change in IL-17 between ESAT-6·CFP-10-stimulated vs. unstimulated conditions. *p < 0.05

Adults with a new diagnosis of MDR-TB and DS-TB were enrolled from tuberculosis clinics in Callao, Peru while healthy control participants were recruited from local medicine clinics and community. Participants provided blood samples for peripheral blood mononuclear cells (PBMCs) and plasma isolation. Soluble immune markers including proinflammatory cytokines and immunoglobulins were tested in plasma. PBMCs were analyzed via flow cytometry for immunophenotyping and via cell stimulation assays. To account for false positive rates with 75 distinct cell populations in the immunophenotyping assay Benjamini-Hochberg correction was employed.

Analysis of cell phenotypes identified notable differences. CD8+ T cells were increased in patients with MDR-TB compared to DS-TB (medians (interquartile range) [n]: 51.9 (31.2-65.7) [14] and 27.8 (23.2-34.8) [22], p = 0.036)), and the frequency of CD8+/CD38+ cells were decreased in MDR-TB compared to DS-TB (4.47 (3.3-6.6) [14] and 9.4 (6.2-13.9) [22], p = 0.0057). While analysis of soluble plasma factors did not show significant differences, analysis of cell stimulation assays showed an increased IL-17 production in PBMC from participants with MDR-TB compared to DS-TB when stimulated with the Mtb antigen ESAT6/CFP10 (see Figure; p=0.015).

While much of the immune response to MDR-TB appears similar to DS-TB, we found notable differences, with increased CD8+ T cells, decreased CD8/CD38+ T cells, and increased IL-17 production in response to Mtb stimulation. These data suggest that MDR-TB could prompt differential immune signatures, including expanded IL-17 responses. Further work may lead to better understanding of host-pathogen interactions in MDR-TB disease and possible optimized therapies.

All Authors: No reported disclosures

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