Impaired responsiveness to Gram-negative bacterial infection followed by antibiotic therapy in the absence of TLR2/TLR4 expression. (A–C) Wild-type (white bars, ⋄), TLR2^−/− (light gray bars, □), TLR4^−/− (dark gray bars, •), and TLR2^−/−/TLR4^−/− (black bars, ▴; A) macrophages or mice (B and C) were infected with S. enterica (A and B) or E. coli (A and C) and subjected to antibiotic therapy after 1 h (A–C). (A) Cell culture supernatants were analyzed for TNF-α content by ELISA 16 h after challenge or infection as indicated (Pam₃CSK₄, tripalmitoylated hexapeptide; ND, not detected). (B and C) Mice were infected with 10⁹ CFU S. enterica (ent.) or 5 × 10⁹ CFU E. coli. *, P < 0.003; **, P < 0.052; P values result from comparison to results of respective TLR2^−/−/TLR4^−/− group analysis; n = 5 for each experimental group.