{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:30:29Z","timestamp":1790937029681,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,8,3]]},"abstract":"<jats:p>\n                    Innate and adaptive immunity depends critically on host recognition of pathogen-associated molecules. Toll-like receptors (TLRs) are key mediators of pathogen surveillance at the cell or phagocytic vacuole surface. However, mechanisms underlying recognition of pathogens in other cellular compartments remain unclear, and responses elicited by cytosolic challenge are poorly characterized. We therefore used mouse cDNA microarrays to investigate gene expression triggered by infection of bone marrow-derived macrophages with cytosol- and vacuole-localized\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    (\n                    <jats:italic>Lm<\/jats:italic>\n                    ), a model cytosolic pathogen. The resulting gene expression program included two basic categories of induced genes: an \u201cearly\/persistent\u201d cluster consistent with NF-\u03baB-dependent responses downstream of TLRs, and a subsequent \u201clate response\u201d cluster largely composed of IFN-responsive genes (IRGs). The early\/persistent cluster was observed upon infection with WT, heat-killed, or mutant\n                    <jats:italic>Lm<\/jats:italic>\n                    lacking listeriolysin O, the pore-forming hemolysin that promotes escape from phagocytic vacuoles. However, the IRG cluster depended on entry of WT\n                    <jats:italic>Lm<\/jats:italic>\n                    into the cytosol. Infection with listeriolysin O-expressing, cytosolic\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    (\n                    <jats:italic>Bs<\/jats:italic>\n                    ) strikingly recapitulated the expression profile associated with WT\n                    <jats:italic>Lm<\/jats:italic>\n                    , including IRG induction. IRG up-regulation was associated with MyD88-independent induction of IFN-\u03b2 transcription and activity. Whereas\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (\n                    <jats:italic>Sa<\/jats:italic>\n                    ) lipoteichoic acid treatment confirmed that many late-response genes could also be stimulated through TLRs, our study identified a cytosol-specific transcriptional program independent of TLR signaling through MyD88. Further characterization of cytosolic surveillance pathway(s) and their points of convergence with TLR- and IFN-dependent pathways will enhance our understanding of the means by which mammals detect and respond to pathogens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0403215101","type":"journal-article","created":{"date-parts":[[2004,7,21]],"date-time":"2004-07-21T22:45:03Z","timestamp":1090449903000},"page":"11386-11391","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["A specific gene expression program triggered by Gram-positive bacteria in the cytosol"],"prefix":"10.1073","volume":"101","author":[{"given":"Ramona L.","family":"McCaffrey","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fawcett","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"O'Riordan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Dall","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Havell","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick O.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Portnoy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, CA 94720-3202; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0663; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109; and Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,7,21]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35100529"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(01)00304-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(02)02145-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1086"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202476699"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200205009"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.829"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231625398"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-4-1-r2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5543.870"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.15.11181"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022649799"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.7.2710-2717.1992"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.4.1459"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.13.7249"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg078"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/153.5.960"},{"key":"e_1_3_2_20_2","first-page":"879","volume":"4","year":"1993","unstructured":"Wagner, A. 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