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Association of Human TLR1 and TLR6 Deficiency with Altered Immune Responses to BCG Vaccination in South African Infants

Figure 6

TLR1/6 polymorphisms are associated with decreased lipopeptide-induced IL-6 and IL-10 production in PBMCs.

PBMCs from individuals with polymorphisms in TLR6_C745T and TLR1_T1805G were stimulated for 20 hours with TLR ligands LPS (10 ng/mL), PAM2CSK4 (250 ng/mL), or PAM3CSK4 (250 ng/mL). Supernatant IL-6 and IL-10 levels were quantified by ELISA. TLR1 and TLR6 genotypes are designated based on functionality as: TLR1_low (genotype TLR1_1805GG, n = 22), TLR1_high (1805GT/TT, n = 25), TLR6_low (TLR6_745CT/TT, n = 24), or TLR6_high (745CC, n = 23). TLR1/6 diplotypes are designated as TLR1/6_low (TLR1_1805GG and TLR6_745CT/TT, n = 18) or TLR1/6_high (TLR1_1805GT/TT and TLR6_745CC, n = 18). Panels: For IL-6, TLR1/6_low vs high diplotypes (A), TLR6_low versus high genotypes for (B), and TLR1_low versus high genotypes for IL-6 (C). For IL-10, TLR1/6_low vs high diplotypes for media, PAM2, and PAM3 (D) or LPS (E); TLR6_low versus high genotypes for media, PAM2, and PAM3 (F) or LPS (G); TLR1_low versus high genotypes for media, PAM2, and PAM3 (H) or LPS (I). Diplotypes and genotypes with normal signaling (high) designated with a box with dots while deficient signaling (low) designated with clear box. P values represent significant differences as assessed by a Mann-Whitney U-test for comparison of low versus high groups. *P<0.05, **P<0.01, ***P≤0.001.

Figure 6

doi: https://doi.org/10.1371/journal.ppat.1002174.g006