With rising age (TLR3 and -4; P 0.04 by Kruskal-Wallis; Fig. 1). In contrast, TNF- and IFN- production in response to these 3 agonists was weak at birth after which elevated significantly to reachTABLE two Univariate evaluation of spontaneous and TLR agonist-mediated cytokine responses in cord/infant entire blood as a function of P. falciparum infection detected either inside the mother at delivery or in the course of infancyaCytokine and P. falciparum infectionb IL-6 Mother (at delivery) Infant M0-M3 M4-M6 M7-M12 IL-10 Mother (at delivery) Infant M0-M3 M4-M6 M7-M12 TNFMother (at delivery) Infant M0-M3 M4-M6 M7-Ma bTLR3 Coefficient (SD) 39,697 (18,685) 7,969 (35,165) 13,092 (26,431) 15,297 (17,943) P 0.02 NS NS NSTLR4 Coefficient (SD) 23,266 (17,497) 18,425 (32,309) 31,224 (24,277) 1,602 (16,736) P 0.04 NS 0.07 NSTLR7/8 Coefficient (SD) 15,335 (22,503) 64,449 (40,690) 34,977 (30,934) 8,256 (21,346) P NS 0.06 NS NSTLR9 Coefficient (SD) eight,615 (9,930) 16,961 (17,797) 9,364 (13,902) 11,586 (9,569) P NS NS NS NSUnstimulated Coefficient (SD) 0.two (0.4) 0.7 (0.eight) 0.three (0.6) 0.two (0.four) P NS NS NS NS623 (283) 136 (534) 191 (402) 300 (272)0.01 NS NS NS325 (274) 438 (499) 31 (379) 297 (261)NS NS NS NS191 (520) 64 (948) 596 (715) 1,133 (483)NS 0.06 NS 0.98 (278) 759 (497) 301 (389) 159 (267)0.02 0.05 NS NS0.1 (0.4) 0.1 (0.8) 0.five (0.six) 0.4 (0.4)NS NS NS NS1,772 (941) 1,747 (1,741) 298 (1,312) 535 (891)0.01 NS NS NS2,005 (1,207) 1,347 (two,202) 1,194 (1,671) 1,268 (1,151)0.06 NS NS 0.4,023 (two,807) 992 (5,080) 3,363 (3,854) 1,739 (2,666)0.08 NS NS NS334 (921) 1,016 (1,652) 1,777 (1,288) 1,029 (885)NS NS NS 0.0.1 (0.4) 0.three (0.7) 0.five (0.five) 0.2 (0.4)NS NS NS NSPositive/negative coefficients indicate cytokine concentrations above/below handle (uninfected) levels. SD, standard deviation; NS, not significant. “Mother (at delivery)” denotes the influence of infection at delivery or inside the time period ten days prior to delivery on neonatal/infant cytokine responses inside the initially 12 months of life. “Infant” denotes the influence of infection throughout different periods of early life on spontaneous or TLR stimulation-mediated cytokine responses over the whole 12-month period.152120-54-2 Price M0, cord blood; M3, M6, M12, blood drawn at 3, six, 12 months of age, respectively.Formula of 470482-44-1 August 2013 Volume 81 Numberiai.PMID:33608982 asm.orgGb and?et al.FIG 1 Spontaneous and TLR agonist-mediated cytokine production in neonatal/infant entire blood. In each and every case, agonist-mediated responses presented are these following subtraction of the corresponding cytokine concentrations in supernatants of unstimulated cells. Box plots illustrate medians with 25th and 75th percentiles and whiskers for 10th and 90th percentiles. M0, cord blood; M3, M6, M12, peripheral venous blood at 3, six, 12 months of age, respectively; Unsti, unstimulated samples. The statistical significance of variations in cytokine activity detected at different ages was determined applying the nonparametric KruskalWallis test. *, P 0.05; **, P 0.01; ***, P 0.001.iai.asm.orgInfection and ImmunityMalaria Modifies Early-Life TLR Cytokine ResponsesTABLE 3 Multivariate (LMM) analyses of alterations in spontaneous and TLR-mediated cytokine responses in entire blood as a function of infants’ age and of maternal P. falciparum infection at deliveryaTLR3 Cytokine and P. falciparum infection IL-6 Infant age (mo) 3 six 12 Mother at delivery and: M0 M3 M6 M12 IL-10 Infant age (mo) three 6 12 Mother at delivery and: M0 M3 M6 M12 TNF Infant age (mo) three six 12 Mother at delivery and: M0 M3 M6 MaTLR4.