{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:49:23Z","timestamp":1792075763068,"version":"4.4.0"},"reference-count":93,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2005,8,1]],"date-time":"2005-08-01T00:00:00Z","timestamp":1122854400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2005,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The fungal pathogen<jats:italic>Cryptococcus neoformans<\/jats:italic>survives phagocytosis by macrophages and proliferates within, ultimately establishing latent infection as a facultative intracellular pathogen that can escape macrophage control to cause disseminated disease. This process is hypothesized to be important for<jats:italic>C. neoformans<\/jats:italic>pathogenesis; however, it is poorly understood how<jats:italic>C. neoformans<\/jats:italic>adapts to and overcomes the hostile intracellular environment of the macrophage. Using DNA microarray technology, we have investigated the transcriptional response of<jats:italic>C. neoformans<\/jats:italic>to phagocytosis by murine macrophages. The expression profiles of several genes were verified using quantitative reverse transcription-PCR and a green fluorescent protein reporter strain. Multiple membrane transporters for hexoses, amino acids, and iron were up-regulated, as well as genes involved in responses to oxidative stress. Genes involved in autophagy, peroxisome function, and lipid metabolism were also induced. Interestingly, almost the entire mating type locus displayed increased expression 24 h after internalization, suggesting an intrinsic connection between infection and the<jats:italic>MAT<\/jats:italic>locus. Genes in the Gpa1-cyclic AMP-protein kinase A pathway were also up-regulated. Both<jats:italic>gpa1<\/jats:italic>and<jats:italic>pka1<\/jats:italic>mutants were found to be compromised in macrophage infection, confirming the important role of this virulence pathway. A large proportion of the repressed genes are involved in ribosome-related functions, rRNA processing, and translation initiation\/elongation, implicating a reduction in translation as a central response to phagocytosis. In summary, this gene expression profile allows us to interpret the adaptation of<jats:italic>C. neoformans<\/jats:italic>to the intracellular infection process and informs the search for genes encoding novel virulence attributes.<\/jats:p>","DOI":"10.1128\/ec.4.8.1420-1433.2005","type":"journal-article","created":{"date-parts":[[2005,8,8]],"date-time":"2005-08-08T19:33:07Z","timestamp":1123529587000},"page":"1420-1433","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":175,"title":["<i>Cryptococcus neoformans<\/i>Gene Expression during Murine Macrophage Infection"],"prefix":"10.1128","volume":"4","author":[{"given":"Weihua","family":"Fan","sequence":"first","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Kraus","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Josee","family":"Boily","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"},{"name":"Pharmacology and Cancer Biology"},{"name":"Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01852.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.7.2291-2296.1991"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.1998.1079"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.29"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.3.422-430.2003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.4.1418"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1437"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"Casadevall A. and J. Perfect. 1998. Cryptococcus neoformans . American Society for Microbiology Washington D.C.","DOI":"10.1128\/9781555818241"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.7.4912-4919.1994"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.871"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094226"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.3.5.570-574.1996"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02375.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.2001.2405"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02236.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.443-448.2000"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02213.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03563.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2003.10.029"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.5.1067-1075.2004"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1812-1820.1999"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5338.680"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.9.3179-3191.2001"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2001.tb00582.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-145-9-2415"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92283-N"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4225-4237.2000"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(01)02035-2"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02295.x"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020384"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.1.46-54.2005"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2004.09.003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03365.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-5-76"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.36.052402.152652"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/35044114"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.2.420-429.2004"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02651.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1105\/TPC.010084"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.5.1249-1260.2004"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.2.602-605.1992"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.150.3.1414-1421.1982"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.8.2125-2133.2000"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.64.4.746-785.2000"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.5.704-718.2002"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04474.x"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.6034-6039.1999"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103773"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.5.1076-1087.2004"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/35083594"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.5.1236"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.856001"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.1.202-208.2005"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.03921.x"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.6.1513-1524.2004"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03059.x"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-05-0370"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.148.3.465"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.10.2576"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2004.04.001"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.998"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.1.190-201.2005"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01389.x"},{"key":"e_1_3_2_67_2","doi-asserted-by":"crossref","first-page":"898","DOI":"10.4049\/jimmunol.114.2_Part_2.898","volume":"114","year":"1975","unstructured":"Ralph, P., J. Prichard, and M. Cohn. 1975. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J. Immunol.114:898-905.","journal-title":"J. Immunol."},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5468.1062"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.01.1.11-21.2002"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834481100"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5684-5694.2002"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.34.1.623"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.10.3091"},{"key":"e_1_3_2_74_2","first-page":"321","volume":"382","year":"2001","unstructured":"Sharma, C. B., R. Knauer, and L. Lehle. 2001. Biosynthesis of lipid-linked oligosaccharides in yeast: the ALG3 gene encodes the Dol-P-Man:Man5GlcNAc2-PP-Dol mannosyltransferase. Biol. Chem.382:321-328.","journal-title":"Biol. Chem."},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.3.366-377.2002"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03680.x"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-10-2715"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.80202"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261418798"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20074"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02907-8"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01039.x"},{"key":"e_1_3_2_83_2","first-page":"1703","volume":"12","year":"2000","unstructured":"Thines, E., R. W. Weber, and N. J. Talbot. 2000. MAP kinase and protein kinase A-dependent mobilization of triacylglycerol and glycogen during appressorium turgor generation by Magnaporthe grisea. Plant Cell12:1703-1718.","journal-title":"Plant Cell"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052702799"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20073"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.5.1663"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.56.012302.160847"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.2.257-272.2002"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.8.3131-3136.1995"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-1-191"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.23.7243-7247.1999"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.11.6155-6164.2003"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-3-31"}],"container-title":["Eukaryotic Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/EC.4.8.1420-1433.2005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/EC.4.8.1420-1433.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T17:32:08Z","timestamp":1706463128000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/EC.4.8.1420-1433.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8]]},"references-count":93,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2005,8]]}},"alternative-id":["10.1128\/EC.4.8.1420-1433.2005"],"URL":"https:\/\/doi.org\/10.1128\/ec.4.8.1420-1433.2005","relation":{},"ISSN":["1535-9778","1535-9786"],"issn-type":[{"value":"1535-9778","type":"print"},{"value":"1535-9786","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8]]},"assertion":[{"value":"2005-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-06-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}