Table 1_Inflammasome-associated immune dysregulation in TB–HIV coinfection.docx

Associations were evaluated using multivariable linearregression and partial Pearson correlation analyses.</p>Results<p>TB–HIV co-infected individuals showed significantly higher expression of AIM2, CASP1, GSDMD, IL1β, and IL18 compared to all other groups (all P < 0.01), while NLRP3 expression remained unchanged. Elevated plasma levels of IL-6, IL-18, and IL-33 further supported a systemic inflammatory profile in the TB-HIV co-infection group.

Strong positive correlations were observed among AIM2, CASP1, GSDMD, IL1β, and IL18 gene expressions at baseline (r= 0.853–0.965), and, to a lesser extent, among them and IL-6 and IL-18 cytokines (r= 0.440-0.645), indicating a coordinated inflammasome-related transcriptional profile, whereas NLRP3 showed no or weak associations. Longitudinal analysis revealed significant reductions in AIM2, CASP1, GSDMD, IL18, and IL1B expression from baseline to week 2, after two weeks of anti-TB therapy and before ART initiation, and from baseline to week 6, after six weeks of anti-TB therapy and four weeks of ART (all P < 0.05).</p>Conclusions<p>TB–HIV coinfection was characterized by distinct inflammasome-related transcriptional and inflammatory profiles, highlighting AIM2 as a potential pathway for further investigation.

Our findings indicate that TB–HIV coinfection is associated with a coordinated inflammasome-related transcriptional and cytokine profile, characterized by increased expression of AIM2 and downstream effector genes, without detectable changes in NLRP3 transcript abundance.</p>