The M. genitalium -induced inflammatory cytokine secretion from human monocyte-derived macrophages was mediated predominately by proteins. Human MDM were exposed to viable M. genitalium G37 (MOI 10) or viable M. genitalium that had been denatured by heat or digested with proteinase-K (MOI 10). Cytokine secretion was quantified from culture supernatants collected 6 h following exposure as described in the Methods. Data shown are the mean ± SEM of IL-6 (a representative acute-phase cytokine) induction from a typical experiment using M. genitalium strain G37 performed in triplicate wells compared to vehicle control (PBS) wells analyzed in parallel for each cell type. Data collected for each experiment using strain G37 or M2300 were similar in pattern and magnitude between 2 additional blood donors. *, p < 0.01 vs. PBS control using ANOVA. f, p < 0.01 vs. viable M. genitalium G37.