0 11 Attenuation attenuation NN 12 14 of of IN 15 20 gamma gamma NN 21 39 interferon-induced interferon-induced JJ 40 48 tyrosine tyrosine NN 49 64 phosphorylation phosphorylation NN 65 67 in in IN 68 79 mononuclear mononuclear JJ 80 90 phagocytes phagocyte NNS 91 99 infected infect VBN 100 104 with with IN 105 115 Leishmania Leishmania NNP 116 124 donovani donovani NNS 124 125 : : : 126 135 selective selective JJ 136 146 inhibition inhibition NN 147 149 of of IN 150 159 signaling signaling NN 160 167 through through IN 168 173 Janus Janus NNP 174 181 kinases kinase NNS 182 185 and and CC 186 191 Stat1 stat1 NN 191 192 . . . 194 197 The the DT 198 207 induction induction NN 208 210 of of IN 211 215 gene gene NN 216 229 transcription transcription NN 230 232 in in IN 233 241 response response NN 242 244 to to TO 245 250 gamma gamma NN 251 261 interferon interferon NN 262 264 is be VBZ 265 273 impaired impaired JJ 274 276 in in IN 277 288 mononuclear mononuclear JJ 289 299 phagocytes phagocyte NNS 300 308 infected infect VBN 309 313 with with IN 314 324 Leishmania Leishmania NNP 325 333 donovani donovani NNS 333 334 , , , 335 338 and and CC 339 342 the the DT 343 353 mechanisms mechanism NNS 354 362 involved involve VBN 363 366 are be VBP 367 370 not not RB 371 376 fully fully RB 377 387 understood understand VBN 387 388 . . . 389 392 The the DT 393 400 changes change NNS 401 403 in in IN 404 408 gene gene NN 409 419 expression expression NN 420 427 brought bring VBD 428 433 about about RP 434 436 by by IN 437 442 gamma gamma NN 443 453 interferon interferon NN 454 457 are be VBP 458 465 thought think VBN 466 468 to to TO 469 476 involve involve VB 477 486 transient transient JJ 487 496 increases increase NNS 497 499 in in IN 500 503 the the DT 504 514 activities activity NNS 515 517 of of IN 518 526 cellular cellular JJ 527 534 protein protein NN 535 543 tyrosine tyrosine NN 544 551 kinases kinase NNS 551 552 , , , 553 562 including include VBG 563 566 the the DT 567 572 Janus Janus NNP 573 580 kinases kinase NNS 581 585 Jak1 jak1 NN 586 589 and and CC 590 594 Jak2 jak2 NN 594 595 , , , 596 603 leading lead VBG 604 606 to to TO 607 615 tyrosine tyrosine NN 616 631 phosphorylation phosphorylation NN 632 634 of of IN 635 638 the the DT 639 652 transcription transcription NN 653 659 factor factor NN 660 665 Stat1 stat1 NN 665 666 . . . 667 669 To to TO 670 681 investigate investigate VB 682 685 the the DT 686 696 mechanisms mechanism NNS 697 707 accounting account VBG 708 711 for for IN 712 715 the the DT 716 724 impaired impaired JJ 725 734 responses response NNS 735 737 to to TO 738 743 gamma gamma NN 744 754 interferon interferon NN 754 755 , , , 756 757 a a DT 758 763 model model NN 764 770 system system NN 771 774 for for IN 775 784 examining examine VBG 785 792 overall overall JJ 793 800 changes change NNS 801 803 in in IN 804 811 protein protein NN 812 820 tyrosine tyrosine NN 821 836 phosphorylation phosphorylation NN 836 837 , , , 838 848 activation activation NN 849 851 of of IN 852 856 Jak1 Jak1 NNP 857 860 and and CC 861 865 Jak2 jak2 NN 866 869 and and CC 870 885 phosphorylation phosphorylation NN 886 888 of of IN 889 894 Stat1 Stat1 NNP 895 898 was be VBD 899 908 developed develop VBN 909 911 in in IN 912 919 phorbol phorbol NN 920 932 12-myristate 12-myristate NN 933 958 13-acetate-differentiated 13-acetate-differentiated JJ 959 964 U-937 u-937 NN 965 970 cells cell NNS 970 971 . . . 972 980 Analysis Analysis NNP 981 983 of of IN 984 994 whole-cell whole-cell JJ 995 1002 lysates lysate NNS 1003 1005 by by IN 1006 1025 antiphosphotyrosine antiphosphotyrosine NN 1026 1040 immunoblotting immunoblotting NN 1041 1047 showed show VBD 1048 1052 that that IN 1053 1063 incubation incubation NN 1064 1068 with with IN 1069 1074 gamma gamma NN 1075 1085 interferon interferon NN 1086 1093 brought bring VBD 1094 1099 about about RP 1100 1108 specific specific JJ 1109 1118 increases increase NNS 1119 1121 in in IN 1122 1137 phosphotyrosine phosphotyrosine NN 1138 1146 labeling labeling NN 1147 1149 of of IN 1150 1157 several several JJ 1158 1166 proteins protein NNS 1166 1167 . . . 1168 1177 Increased increase VBN 1178 1186 labeling labeling NN 1187 1189 of of IN 1190 1195 these these DT 1196 1204 proteins protein NNS 1205 1213 occurred occur VBD 1214 1216 to to TO 1217 1224 similar similar JJ 1225 1232 extents extent NNS 1233 1235 in in IN 1236 1243 control control NN 1244 1249 cells cell NNS 1250 1253 and and CC 1254 1256 in in IN 1257 1262 cells cell NNS 1263 1267 that that WDT 1268 1271 had have VBD 1272 1276 been be VBN 1277 1285 infected infect VBN 1286 1290 with with IN 1291 1293 L. L. NNP 1294 1302 donovani donovani NNS 1303 1306 for for IN 1307 1309 16 16 CD 1310 1312 h. h. NN 1313 1317 Jak1 jak1 NN 1317 1318 , , , 1319 1323 Jak2 Jak2 NNP 1323 1324 , , , 1325 1328 and and CC 1329 1334 Stat1 Stat1 NNP 1335 1339 were be VBD 1340 1358 immunoprecipitated immunoprecipitate VBN 1359 1363 from from IN 1364 1371 control control NN 1372 1375 and and CC 1376 1394 interferon-treated interferon-treated JJ 1395 1400 cells cell NNS 1400 1401 , , , 1402 1405 and and CC 1406 1414 tyrosine tyrosine NN 1415 1430 phosphorylation phosphorylation NN 1431 1433 of of IN 1434 1439 these these DT 1440 1448 proteins protein NNS 1448 1449 , , , 1450 1458 detected detect VBN 1459 1461 by by IN 1462 1481 antiphosphotyrosine antiphosphotyrosine NN 1482 1496 immunoblotting immunoblotting NN 1497 1500 was be VBD 1501 1505 used use VBN 1506 1508 to to TO 1509 1517 measured measure VBN 1518 1523 their their PRP$ 1524 1534 activation activation NN 1534 1535 . . . 1536 1544 Tyrosine Tyrosine NNP 1545 1560 phosphorylation phosphorylation NN 1561 1563 of of IN 1564 1568 Jak1 Jak1 NNP 1568 1569 , , , 1570 1574 Jak2 Jak2 NNP 1574 1575 , , , 1576 1579 and and CC 1580 1585 Stat1 Stat1 NNP 1586 1595 increased increase VBD 1596 1604 markedly markedly RB 1604 1605 , , , 1606 1608 in in IN 1609 1610 a a DT 1611 1625 dose-dependent dose-dependent JJ 1626 1632 manner manner NN 1632 1633 , , , 1634 1636 in in IN 1637 1642 U-937 u-937 NN 1643 1648 cells cell NNS 1649 1658 incubated incubate VBN 1659 1663 with with IN 1664 1669 gamma gamma NN 1670 1680 interferon interferon NN 1680 1681 . . . 1682 1684 In in IN 1685 1693 contrast contrast NN 1693 1694 , , , 1695 1697 in in IN 1698 1703 cells cell NNS 1704 1712 infected infect VBN 1713 1717 with with IN 1718 1720 L. L. NNP 1721 1729 donovani donovani NNS 1729 1730 , , , 1731 1739 tyrosine tyrosine NN 1740 1755 phosphorylation phosphorylation NN 1756 1758 of of IN 1759 1763 Jak1 Jak1 NNP 1763 1764 , , , 1765 1769 Jak2 Jak2 NNP 1769 1770 , , , 1771 1774 and and CC 1775 1780 Stat1 Stat1 NNP 1781 1784 was be VBD 1785 1793 markedly markedly RB 1794 1802 impaired impaired JJ 1802 1803 . . . 1804 1808 This this DT 1809 1815 effect effect NN 1816 1819 was be VBD 1820 1829 dependent dependent JJ 1830 1834 upon upon IN 1835 1838 the the DT 1839 1847 duration duration NN 1848 1850 of of IN 1851 1859 exposure exposure NN 1860 1862 to to TO 1863 1865 L. L. NNP 1866 1874 donovani donovani NNS 1875 1878 and and CC 1879 1882 was be VBD 1883 1890 maximal maximal JJ 1891 1894 and and CC 1895 1903 complete complete JJ 1904 1906 at at IN 1907 1909 16 16 CD 1910 1912 h. h. NN 1913 1920 Results result NNS 1921 1928 similar similar JJ 1929 1931 to to TO 1932 1937 those those DT 1938 1946 observed observe VBN 1947 1951 with with IN 1952 1957 U-937 u-937 NN 1958 1963 cells cell NNS 1964 1968 were be VBD 1969 1973 also also RB 1974 1982 obtained obtain VBN 1983 1987 with with IN 1988 1993 human human JJ 1994 2004 peripheral peripheral JJ 2005 2010 blood blood NN 2011 2020 monocytes monocyte NNS 2020 2021 . . . 2022 2027 These these DT 2028 2036 findings finding NNS 2037 2045 indicate indicate VBP 2046 2050 that that IN 2051 2060 infection infection NN 2061 2063 of of IN 2064 2069 human human JJ 2070 2081 mononuclear mononuclear JJ 2082 2092 phagocytes phagocyte NNS 2093 2097 with with IN 2098 2100 L. L. NNP 2101 2109 donovani donovani NNP 2110 2115 leads lead VBZ 2116 2118 to to TO 2119 2127 impaired impaired JJ 2128 2133 gamma gamma NN 2134 2153 interferon-mediated interferon-mediated JJ 2154 2162 tyrosine tyrosine NN 2163 2178 phosphorylation phosphorylation NN 2179 2182 and and CC 2183 2192 selective selective JJ 2193 2200 effects effect NNS 2201 2203 on on IN 2204 2207 the the DT 2208 2217 Jak-Stat1 jak-stat1 NN 2218 2225 pathway pathway NN 2225 2226 . . . 2227 2243 Unresponsiveness unresponsiveness NN 2244 2246 to to TO 2247 2252 gamma gamma NN 2253 2263 interferon interferon NN 2264 2267 for for IN 2268 2278 activation activation NN 2279 2281 of of IN 2282 2286 this this DT 2287 2294 pathway pathway NN 2295 2298 may may MD 2299 2306 explain explain VB 2307 2315 impaired impaired JJ 2316 2331 transcriptional transcriptional JJ 2332 2341 responses response NNS 2342 2344 in in IN 2345 2364 leishmania-infected leishmania-infected JJ 2365 2370 cells cell NNS 2370 2371 . . .