Table 4.
Network, gene | W1:W0 ratio | W2:W0 ratio | W3:W0 ratio | W4:W0 ratio | W6:W0 ratio | W19:W0 ratio | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean ± SD | P | Mean ± SD | P | Mean ± SD | P | Mean ± SD | P | Mean ± SD | P | Mean ± SD | P | |
Network (i) | ||||||||||||
IL-1α | 53.7 ± 25.5 | .049a | 9.1 ± 11.3 | .085 | 8.8 ± 15.1 | .154 | 12.4 ± 12.6 | .052 | 17.3 ± 28.6 | .140 | 0.5 ± 0.5 | .418 |
IL-1β | 21.9 ± 1.1 | .001b | 4.4 ± 5.2 | .197 | 0.9 ± 0.6 | .137 | 9.9 ± 15.3 | .167 | 62.5 ± 62.1 | .049a | 1.0 ± 1.0 | .086 |
IL-2 | 33.2 ± 13.9 | .041a | 8.7 ± 7.8 | .062 | 26.9 ± 24.4 | .042a | 26.2 ± 24.1 | .044a | 2.2 ± 1.4 | .285 | 1.1 ± 0.8 | .229 |
IL-3 | 55.6 ± 18.1 | .025a | 34.1 ± 25.5 | .020a | 24.0 ± 17.4 | .019a | 26.9 ± 11.1 | .002b | 19.3 ± 16.0 | .031a | 2.0 ± 2.8 | .320 |
IL-4 | 31.9 ± 1.3 | .005b | 3.5 ± 2.8 | .171 | 15.0 ± 26.2 | .172 | 3.5 ± 2.9 | .174 | 1.5 ± 1.7 | .482 | 0.2 ± 0.2 | .459 |
IL-5 | 47.6 ± 10.0 | .011a | 1.9 ± 0.6 | .020a | 1.1 ± 1.1 | .497 | 3.9 ± 6.1 | .192 | 14.6 ± 25.5 | .165 | 2.9 ± 2.6 | .212 |
IL-6 | 16.7 ± 3.5 | .011a | 17.1 ± 13.3 | .030a | 13.4 ± 20.5 | .148 | 29.7 ± 27.6 | .044a | 4.1 ± 4.3 | .172 | 4.9 ± 6.0 | .336 |
IL-7 | 9.0 ± 8.9 | .189 | 2.9 ± 2.5 | .164 | 1.1 ± 0.8 | .333 | 11.0 ± 18.5 | .171 | 5.1 ± 8.7 | .212 | 3.2 ± 4.3 | .270 |
IL-8 | 24.5 ± 7.0 | .021a | 44.6 ± 39.5 | .035a | 14.7 ± 17.9 | .089 | 52.9 ± 44.3 | .029a | 6.8 ± 9.0 | .125 | 1.7 ± 1.5 | .306 |
IL-9 | 10.6 ± 13.2 | .190 | 4.3 ± 1.9 | .034a | 3.3 ± 2.2 | .087 | 5.6 ± 0.6 | .006b | 2.3 ± 1.3 | .158 | UD | UD |
IL-15 | 15.1 ± 3.2 | .012a | 6.3 ± 5.7 | .060 | 7.1 ± 10.3 | .144 | 11.2 ± 13.8 | .097 | 2.1 ± 0.7 | .021a | 3.1 ± 4.4 | .302 |
IL-16 | 8.2 ± 9.5 | .229 | 8.9 ± 4.3 | .013a | 6.2 ± 6.4 | .137 | 3.4 ± 2.0 | .171 | 14.5 ± 16.1 | .090 | 1.6 ± 1.3 | .180 |
IL-18 | 65.9 ± 3.1 | .001b | 39.9 ± 34.4 | .032a | 81.4 ± 44.5 | .006b | 108.2 ± 52.5 | .003b | 46.5 ± 23.7 | .004b | 3.0 ± 4.0 | .278 |
IL-19 | UD | UD | UD | UD | UD | UD | UD | UD | UD | UD | UD | UD |
IL-22 | 36.7 ± 0.8 | .006b | 58.3 ± 47.0 | .028a | 22.7 ± 15.0 | .020a | 23.3 ± 4.9 | .000b | 10.0 ± 11.3 | .127 | 4.6 ± 6.6 | .257 |
IL-23α | 9.7 ± 9.3 | .159 | 5.5 ± 2.7 | .008b | 3.0 ± 2.2 | .050 | 4.8 ± 2.0 | .004b | 1.7 ± 0.8 | .076 | 1.0 ± 1.4 | .409 |
IFN-α | 51.6 ± 12.6 | .015a | 49.1 ± 42.7 | .032a | 21.0 ± 18.3 | .035a | 33.1 ± 25.5 | .023a | 8.8 ± 10.7 | .096 | 1.1 ± 1.6 | .425 |
IFN-β | 50.5 ± 23.1 | .047a | 36.7 ± 21.9 | .010a | 12.3 ± 16.1 | .091 | 12.5 ± 5.0 | .003b | 3.1 ± 4.1 | .169 | UD | UD |
IFN-γ | 20.4 ± 24.5 | .197 | 18.8 ± 15.7 | .036a | 9.1 ± 7.4 | .049a | 54.6 ± 51.6 | .043a | 9.8 ± 8.4 | .051 | 5.9 ± 6.6 | .240 |
TNF-α | 5.7 ± 4.2 | .123 | 3.3 ± 2.5 | .211 | 3.5 ± 2.6 | .188 | 18.7 ± 21.4 | .084 | 1.4 ± 1.2 | .363 | 4.9 ± 6.9 | .369 |
IL-2Rα | 13.4 ± 14.8 | .176 | 9.7 ± 12.8 | .110 | 16.6 ± 15.7 | .046a | 45.6 ± 40.5 | .035a | 17.4 ± 18.8 | .065 | 1.8 ± 1.0 | .177 |
IL-2Rβ | 23.9 ± 10.6 | .047a | 12.6 ± 10.1 | .047a | 29.3 ± 19.6 | .017a | 24.3 ± 19.1 | .031a | 28.3 ± 24.9 | .042a | 5.6 ± 7.3 | .364 |
IL-2Rγ | 20.1 ± 6.3 | .025a | 32.7 ± 29.8 | .039a | 28.3 ± 18.9 | .014a | 31.3 ± 16.2 | .005b | 17.1 ± 9.1 | .006b | 1.6 ± 1.0 | .259 |
IL-3Rα | 25.8 ± 8.6 | .037a | 12.5 ± 8.1 | .028a | 13.6 ± 8.5 | .024a | 17.0 ± 7.2 | .004b | 9.6 ± 12.5 | .160 | 0.4 ± 0.6 | .140 |
IL-4R | 18.5 ± 14.1 | .111 | 21.1 ± 20.3 | .048a | 23.9 ± 12.5 | .005b | 35.9 ± 25.1 | .016a | 15.0 ± 18.5 | .092 | 1.8 ± 2.5 | .358 |
IL-6R | 58.4 ± 10.1 | .008b | 33.1 ± 30.0 | .042a | 44.8 ± 16.5 | .001b | 89.0 ± 61.0 | .015a | 48.4 ± 24.5 | .005b | 1.3 ± 1.8 | .215 |
IL-8Rα | 78.8 ± 89.0 | .171 | 41.2 ± 28.6 | .016a | 50.7 ± 50.1 | .047a | 22.0 ± 8.4 | .001b | 23.5 ± 22.0 | .044a | 0.7 ± 1.0 | .386 |
IL-11Rα | 33.3 ± 25.8 | .112 | 20.7 ± 8.1 | .002b | 20.9 ± 15.5 | .023a | 10.9 ± 1.5 | .000b | 19.7 ± 15.9 | .030a | 9.1 ± 12.8 | .235 |
IL-13Rα1 | 102.0 ± 13.7 | .005b | 34.8 ± 27.5 | .025a | 23.3 ± 21.2 | .040a | 65.2 ± 58.7 | .036a | 25.3 ± 10.7 | .002b | 1.1 ± 1.5 | .494 |
IL-17R | 15.7 ± 14.2 | .141 | 12.9 ± 9.2 | .023a | 8.3 ± 4.3 | .009b | 21.6 ± 17.4 | .029a | 9.2 ± 3.6 | .002b | 4.7 ± 6.6 | .284 |
IL-18R1 | 47.5 ± 16.0 | .027a | 23.4 ± 19.9 | .033a | 32.7 ± 12.9 | .001b | 54.4 ± 38.8 | .017a | 25.6 ± 12.7 | .004b | 1.0 ± 0.9 | .480 |
IFN-γR | 32.9 ± 8.6 | .017a | 17.7 ± 13.6 | .043a | 15.4 ± 3.5 | .001b | 34.3 ± 25.5 | .026a | 9.0 ± 4.5 | .044a | 0.3 ± 0.4 | .095 |
TNFR | 16.2 ± 3.6 | .013a | 10.7 ± 14.4 | .112 | 10.9 ± 9.6 | .043a | 18.0 ± 10.7 | .009b | 8.3 ± 10.5 | .106 | 0.3 ± 0.5 | .242 |
Network (ii) | ||||||||||||
CCL27 | 19.7 ± 5.2 | .024a | 5.6 ± 3.0 | .025a | 2.9 ± 1.4 | .126 | 22.5 ± 30.6 | .110 | 2.0 ± 0.9 | .315 | 4.3 ± 6.0 | .262 |
CCL28 | 58.3 ± 18.1 | .026a | 26.2 ± 29.0 | .072 | 11.4 ± 9.0 | .044a | 14.9 ± 4.9 | .002b | 4.1 ± 4.0 | .193 | 6.8 ± 9.7 | .236 |
GCP2 | 32.9 ± 9.2 | .019a | 59.8 ± 54.8 | .038a | 23.5 ± 22.2 | .045a | 27.9 ± 11.8 | .002b | 8.0 ± 8.2 | .074 | 4.9 ± 6.9 | .288 |
IP-10 | 33.0 ± 4.4 | .013a | 22.0 ± 26.5 | .099 | 7.1 ± 5.9 | .119 | 22.5 ± 19.6 | .047a | 7.9 ± 3.1 | .033a | 7.0 ± 9.9 | .254 |
MCP1 | 20.6 ± 5.4 | .018a | 22.6 ± 14.5 | .013a | 9.0 ± 10.7 | .094 | 16.5 ± 20.6 | .091 | 6.9 ± 7.9 | .094 | 0.9 ± 0.8 | .454 |
MCP2 | 15.6 ± 15.2 | .154 | 35.4 ± 33.0 | .041a | 4.9 ± 1.4 | .001b | 20.9 ± 19.2 | .042a | 6.1 ± 6.9 | .096 | 2.2 ± 2.6 | .291 |
MDC | 25.6 ± 8.5 | .027a | 23.1 ± 20.5 | .037a | 4.5 ± 3.6 | .050 | 16.1 ± 11.9 | .022a | 3.3 ± 4.8 | .176 | 6.0 ± 8.5 | .246 |
MIP-1β | 19.1 ± 18.6 | .151 | 15.3 ± 17.7 | .079 | 17.1 ± 19.0 | .070 | 22.1 ± 17.1 | .024a | 7.0 ± 5.9 | .044a | 0.6 ± 0.8 | .270 |
CCR4 | 24.4 ± 18.9 | .111 | 33.5 ± 21.6 | .012a | 14.2 ± 7.4 | .006b | 16.4 ± 9.3 | .008b | 9.7 ± 7.5 | .031a | 3.6 ± 5.1 | .279 |
CCR5 | 37.8 ± 11.6 | .032a | 42.5 ± 38.3 | .042a | 27.4 ± 23.7 | .043a | 36.4 ± 32.6 | .043a | 15.1 ± 7.3 | .011a | 1.4 ± 2.0 | .494 |
CCR8 | 23.6 ± 0.8 | .002b | 23.6 ± 10.9 | .003b | 15.9 ± 13.9 | .040a | 16.9 ± 15.6 | .046a | 6.2 ± 9.6 | .171 | 4.3 ± 6.1 | .248 |
CCR9 | 43.1 ± 16.0 | .036a | 19.5 ± 17.1 | .041a | 6.6 ± 5.1 | .058 | 22.3 ± 21.1 | .049a | 9.2 ± 7.6 | .049a | 1.1 ± 1.5 | .387 |
CCR10 | 34.0 ± 13.4 | .039a | 19.0 ± 12.3 | .014a | 16.4 ± 10.1 | .013a | 14.6 ± 4.6 | .001b | 5.7 ± 6.4 | .112 | 4.5 ± 6.3 | .244 |
CCR11 | 99.4 ± 3.4 | .002b | 24.1 ± 31.4 | .124 | 5.8 ± 5.5 | .295 | 10.8 ± 12.4 | .165 | 1.7 ± 1.9 | .223 | 2.9 ± 4.1 | .411 |
CXCR4 | 12.2 ± 10.1 | .126 | 9.2 ± 2.3 | .000b | 6.3 ± 3.5 | .011a | 6.5 ± 2.8 | .003b | 2.7 ± 1.3 | .015a | 2.5 ± 1.3 | .141 |
CXCR6 | 13.0 ± 7.8 | .138 | 17.8 ± 13.3 | .037a | 15.4 ± 6.8 | .007b | 16.1 ± 12.8 | .047a | 8.1 ± 8.5 | .155 | 3.9 ± 5.5 | .360 |
XCR1 | 54.0 ± 6.9 | .009b | 12.5 ± 13.2 | .113 | 3.4 ± 2.8 | .461 | 8.8 ± 9.9 | .167 | 1.0 ± 0.5 | .194 | 3.7 ± 5.3 | .286 |
MIF | 14.4 ± 13.2 | .144 | 12.3 ± 8.7 | .019a | 8.3 ± 4.0 | .005b | 9.2 ± 7.2 | .031a | 4.0 ± 1.6 | .004b | 1.9 ± 2.7 | .315 |
ISG15 | 0.7 ± 0.5 | .263 | 4.0 ± 5.5 | .157 | 5.3 ± 2.0 | .003b | 5.1 ± 2.4 | .008b | 2.0 ± 2.4 | .209 | 1.0 ± 1.3 | .496 |
Network (iii) | ||||||||||||
B7-2 | 48.8 ± 18.3 | .039a | 51.1 ± 44.1 | .036a | 38.1 ± 17.7 | .004b | 25.5 ± 18.7 | .027a | 17.6 ± 20.5 | .102 | 8.9 ± 12.6 | .249 |
CD28 | 79.2 ± 26.0 | .026a | 75.3 ± 30.5 | .001b | 91.7 ± 48.5 | .005b | 90.9 ± 69.6 | .021a | 39.3 ± 8.9 | .000b | 7.3 ± 10.2 | .229 |
CTLA4 | 18.1 ± 21.6 | .191 | 7.8 ± 5.4 | .020a | 5.2 ± 3.1 | .015a | 5.3 ± 3.1 | .015a | 2.2 ± 0.6 | .014a | 2.2 ± 3.2 | .260 |
ICOS | 10.7 ± 14.2 | .218 | 13.5 ± 8.5 | .013a | 33.9 ± 31.8 | .042a | 19.1 ± 15.2 | .027a | 8.3 ± 9.2 | .080 | 2.7 ± 3.8 | .295 |
PDL1 | 5.4 ± 2.0 | .186 | 6.7 ± 4.1 | .031a | 51.5 ± 73.4 | .111 | 14.4 ± 8.3 | .012a | 3.8 ± 4.1 | .175 | 0.3 ± 0.3 | .377 |
PDL2 | 42.0 ± 18.1 | .048a | 33.0 ± 31.6 | .049a | 13.9 ± 11.1 | .041a | 37.7 ± 33.9 | .040a | 7.1 ± 8.4 | .147 | 7.3 ± 10.2 | .239 |
PD1 | 35.0 ± 39.8 | .175 | 15.7 ± 23.1 | .126 | 11.8 ± 8.2 | .019a | 12.4 ± 10.9 | .040a | 13.1 ± 18.6 | .121 | 3.0 ± 4.2 | .293 |
Network (iv) | ||||||||||||
C-MAF | 47.3 ± 21.1 | .045a | 28.8 ± 34.0 | .077 | 15.5 ± 17.6 | .075 | 20.4 ± 21.4 | .060 | 8.4 ± 7.6 | .049a | 1.2 ± 1.7 | .441 |
PU.1 | 49.0 ± 20.2 | .038a | 31.8 ± 23.6 | .022a | 34.4 ± 19.4 | .008b | 47.9 ± 29.3 | .010a | 27.6 ± 24.4 | .039a | 2.3 ± 2.2 | .329 |
SCM1 | 52.4 ± 17.4 | .027a | 13.8 ± 15.0 | .066 | 3.5 ± 2.7 | .048a | 5.9 ± 4.7 | .036a | 1.2 ± 1.0 | .250 | 1.8 ± 2.6 | .243 |
T-bet | 13.1 ± 11.9 | .139 | 6.7 ± 5.5 | .068 | 2.8 ± 1.6 | .205 | 3.5 ± 2.3 | .125 | 1.8 ± 0.6 | .458 | 1.4 ± 0.5 | .066 |
GATA-3 | 3.7 ± 2.6 | .233 | 3.4 ± 3.9 | .148 | 7.6 ± 10.3 | .110 | 4.7 ± 5.6 | .119 | 4.3 ± 4.9 | .118 | UD | UD |
STAT1 | 46.1 ± 17.1 | .032a | 85.7 ± 46.1 | .005b | 75.7 ± 50.7 | .013a | 74.2 ± 37.8 | .004b | 21.4 ± 7.9 | .001b | 7.2 ± 10.1 | .239 |
STAT6 | 12.6 ± 3.1 | .017a | 20.1 ± 16.9 | .032a | 29.5 ± 19.6 | .014a | 65.1 ± 59.7 | .038a | 22.0 ± 17.7 | .028a | 0.5 ± 0.6 | .169 |
FoxP3 | 4.4 ± 4.0 | .391 | 2.5 ± 1.0 | .465 | 2.0 ± 0.4 | .362 | 1.7 ± 0.5 | .302 | 1.1 ± 0.1 | .209 | UD | UD |
Network (v) | ||||||||||||
IFN-γ | 20.4 ± 24.5 | .197 | 18.8 ± 15.7 | .036a | 9.1 ± 7.4 | .049a | 54.6 ± 51.6 | .043a | 9.8 ± 8.4 | .051 | 5.9 ± 6.6 | .240 |
T-bet | 13.1 ± 11.9 | .139 | 6.7 ± 5.5 | .068 | 2.8 ± 1.6 | .205 | 3.5 ± 2.3 | .125 | 1.8 ± 0.6 | .458 | 1.4 ± 0.5 | .066 |
TIM1 | 37.0 ± 14.4 | .039a | 17.6 ± 13.6 | .027a | 10.1 ± 10.7 | .073 | 20.3 ± 12.6 | .014a | 0.5 ± 0.2 | .267 | UD | UD |
TIM3 | 26.3 ± 11.5 | .043a | 5.4 ± 2.2 | .003b | 16.6 ± 22.0 | .083 | 10.5 ± 5.7 | .008b | 2.5 ± 0.6 | .002b | UD | UD |
IP-10 | 33.0 ± 4.4 | .013a | 22.0 ± 26.5 | .099 | 7.1 ± 5.9 | .119 | 22.5 ± 19.6 | .047a | 7.9 ± 3.1 | .033a | 7.0 ± 9.9 | .254 |
Network (vi) | ||||||||||||
GZMA | 70.1 ± 25.1 | .032a | 96.5 ± 92.7 | .044a | 29.0 ± 20.5 | .021a | 117.6 ± 114.5 | .045a | 8.0 ± 7.2 | .091 | 3.6 ± 3.6 | .271 |
GZMK | 15.7 ± 15.7 | .174 | 40.0 ± 28.9 | .019a | 79.1 ± 26.5 | .001b | 149.9 ± 45.7 | .000b | 50.1 ± 42.5 | .032a | 5.0 ± 7.1 | .280 |
Network (vii) | ||||||||||||
TLR2 | 44.9 ± 7.3 | .007b | 16.1 ± 18.6 | .077 | 8.9 ± 4.6 | .007b | 7.8 ± 5.1 | .019a | 12.7 ± 9.1 | .021a | 3.1 ± 4.4 | .284 |
VEGF | UD | UD | 19.8 ± 0.2 | .000b | 19.2 ± 2.6 | .000b | 15.3 ± 0.7 | .000b | 8.2 ± 3.2 | .003b | 4.9 ± 7.0 | .255 |
MMP-9 | 12.3 ± 11.3 | .140 | 12.3 ± 10.7 | .039a | 9.1 ± 7.8 | .040a | 10.9 ± 9.6 | .042a | 1.6 ± 0.4 | .038a | 6.3 ± 8.9 | .256 |
UBP43 | 5.6 ± 1.3 | .019a | 7.8 ± 8.3 | .076 | 4.4 ± 6.5 | .170 | 15.0 ± 20.1 | .107 | 3.2 ± 3.0 | .099 | 2.0 ± 2.0 | .285 |
ICAM-1 | 16.0 ± 11.1 | .098 | 9.5 ± 5.9 | .014a | 7.7 ± 8.2 | .076 | 10.1 ± 7.5 | .027a | 6.8 ± 5.1 | .033a | 4.3 ± 5.9 | .261 |
CTSG | 6.2 ± 5.0 | .327 | 58.1 ± 55.0 | .045a | 62.8 ± 61.0 | .048a | 37.0 ± 30.8 | .033a | 30.1 ± 27.8 | .048a | 8.9 ± 9.8 | .192 |
EDN1 | 47.4 ± 20.3 | .042a | 14.7 ± 8.4 | .008b | 5.1 ± 3.2 | .021a | 8.8 ± 3.6 | .002b | 4.3 ± 4.9 | .116 | 3.5 ± 4.9 | .273 |
SLPI | 40.4 ± 7.5 | .009a | 17.7 ± 19.1 | .066 | 5.4 ± 6.3 | .111 | 12.9 ± 10.2 | .030a | 2.4 ± 2.0 | .110 | 2.2 ± 3.1 | .329 |
NOTE. BCG-induced gene networks were detectable at 1 week after BCG vaccination/infection and were stable over time. Seventy-four genes identified in the initial experiment were longitudinally measured for their expression in peripheral-blood lymphocytes collected from an additional 4 rhesus macaques after intravenous vaccination/infection. Data were calculated as for those in table 3, except that postvaccination expression levels are for multiple time points and that no quantitation was done for genes that were not apparently up-regulated 5 weeks after BCG vaccination (table 3). UD, undetectable; W, week.
P < .05.
P < .01.