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Published on: April 5, 2017
Lineage-Dependent IFN-γ Responses to Drug-Sensitive and Isoniazid-Resistant Mycobacterium tuberculosis Clinical
Yoopie Setiawan1,2, Lidya Chaidir3,4, Robyn Irawan5
1Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia.
Purpose:
Genetic diversity of Mycobacterium tuberculosis (Mtb) contributes to variations in host immune responses. The Modern Beijing (MB) sub-lineage (Lineage 2, L2) has been associated with reduced interferon-gamma (IFN-γ) responses compared with strains from other lineages. However, the influence of drug-resistance status on lineage-specific immune responses remains poorly understood. This study investigated IFN-γ responses induced by clinical Mtb isolates with different lineages and resistance profiles.
Methods:
Peripheral blood mononuclear cells (PBMCs) from 18 healthy adults were stimulated with lysates of clinical Mtb isolates representing the LAM and MB sub-lineages, including drug-sensitive (DS) and isoniazid mono-resistant (Hr-TB) variants. IFN-γ levels were measured using ELISA after 48-hour stimulation. Paired t-tests and two-way repeated-measures ANOVA were used to evaluate the effects of lineage, resistance status, and their interaction on IFN-γ responses.
Results:
MB isolates induced significantly lower IFN-γ levels than LAM isolates (15.30 ± 6.28 vs 19.16 ± 7.28 pg/mL; p < 0.001). Similarly, Hr-TB isolates induced lower IFN-γ responses than DS isolates (15.44 ± 6.39 pg/mL vs 19.02 ± 7.26 pg/mL; p < 0.001). Stratified analysis revealed that within the MB lineage, Hr-TB isolates significantly reduced IFN-γ production compared to DS isolates (13.14 ± 6.13 pg/mL vs 17.45 ± 5.81 pg/mL; p < 0.001). In contrast, no significant difference was observed between DS and Hr-TB isolates within the LAM lineage (p = 0.061). No significant interaction was observed between Mtb lineage and drug-resistance status on IFN-γ responses (p = 0.390).
Conclusion:
These findings demonstrate that IFN-γ responses to Mtb are influenced by both bacterial lineage and drug-resistance status. The MB sub-lineage, particularly in Hr-TB isolates, was associated with reduced IFN-γ production, indicating lineage-associated differences in immunomodulatory capacity. These findings provide insights into TB pathogenesis and may support the development of future vaccine or host-directed therapeutic strategies.
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