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This study investigated whether biological sex differences in immune responses contribute to the higher tuberculosis rates observed in males. Researchers analyzed gene expression data from blood, lung fluid, and skin test samples across multiple TB states (active disease, subclinical, and latent infection) and found that immune responses were largely similar between males and females. The only consistent differences were related to sex chromosome genes rather than immune pathways, suggesting that higher TB rates in males likely result from greater exposure to the bacteria rather than weaker immune defenses.
Why it matters
These findings challenge the assumption that biological immune differences explain sex disparities in tuberculosis incidence. The results suggest that public health interventions should focus on addressing behavioral and social factors that increase male exposure to TB rather than developing sex-specific immunological treatments.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Males incur greater risk of tuberculosis (TB) than females, but the contribution of sex-associated immune differences remains unclear. We addressed this using sex-stratified transcriptomic analyses across four independent studies spanning active pulmonary TB, subclinical TB and latent infection, in peripheral blood, bronchoalveolar lavage (BAL) and by using the tuberculin skin test (TST) as a standardised in vivo antigenic challenge. In blood of active TB patients, expression of TNF- and type I interferon-regulated signatures, genome-wide gene expression, and performance of leading host-response biomarkers of TB were comparable between sexes. Similarly, blood transcriptomic biomarkers showed no meaningful sex-related differences for predicting asymptomatic or incident TB. In the TST of people with latent infection, bulk and single-cell RNA sequencing identified only limited differences, largely restricted to sex chromosome-linked transcripts, with no consistent evidence of dimorphism in immune-regulated pathways. Single-cell RNA sequencing of BAL samples identified reduced abundance of B cells in male TB patients, with gene expression differences again largely restricted to sex chromosome-linked transcripts. These findings suggest that canonical immune responses associated with TB are broadly similar between the sexes, and that increased TB risk among males more likely reflects differential exposure rather than intrinsic immunological susceptibility.
Source: Human in vivo immunology of tuberculosis is not affected by sex dimorphism.