{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:40:42Z","timestamp":1790887242473,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":["Infect Immun"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            is an opportunistic fungal pathogen that causes pneumonia in a variety of clinical settings. An early step in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            infection involves the attachment of organisms to alveolar epithelial cells (AECs). AECs produce chemokines in response to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            stimulation, but the upstream host-pathogen interactions that activate AEC signaling cascades are not well-defined. MyD88 is an adaptor molecule required for activation of proinflammatory signaling cascades following Toll-like receptor (TLR)-dependent recognition of conserved molecular patterns on pathogens. To determine whether the TLR\/MyD88 pathway is required for the AEC chemokine response to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            , wild-type (WT) and MyD88-deficient AECs were incubated with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            . As expected, WT AECs produced CCL2 and CXCL2 following\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            stimulation. In contrast, MyD88-deficient AECs were severely impaired in their ability to respond to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            . MyD88-deficient AECs did not display\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            -induced Jun N-terminal protein kinase activation and produced much less chemokine than\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            -stimulated WT AECs. Using a panel of TLR agonists, primary murine AECs were found to respond vigorously to TLR2 and TLR4 agonists. However, the AEC chemokine response to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            did not require TLR2 or TLR4. Surprisingly, the interleukin-1 receptor (IL-1R) was required for an AEC chemokine response to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            . The role of MyD88 in early responses during\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            infection was supported by\n            <jats:italic>in vivo<\/jats:italic>\n            studies demonstrating that MyD88-deficient mice showed impaired\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            -stimulated chemokine production and impaired inflammatory cell recruitment. These data indicate an important role for MyD88 in the AEC inflammatory response to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/iai.00708-12","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T02:57:31Z","timestamp":1346122651000},"page":"3912-3920","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["The Alveolar Epithelial Cell Chemokine Response to Pneumocystis Requires Adaptor Molecule MyD88 and Interleukin-1 Receptor but Not Toll-Like Receptor 2 or 4"],"prefix":"10.1128","volume":"80","author":[{"given":"Sheila N.","family":"Bello-Irizarry","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Infectious Diseases, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Gigliotti","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA"},{"name":"Department of Pediatrics, Infectious Diseases, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry W.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA"},{"name":"Department of Pediatrics, Infectious Diseases, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80596-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8381"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0078OC"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00067-11"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1999.00517.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.3.713"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.10.010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0300OC"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00157-07"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00668-06"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209715200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020609"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/313843"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-006-9250-x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.12.004"},{"key":"e_1_3_2_17_2","first-page":"70","article-title":"Diagnostic strategies for Pneumocystis carinii pneumonia","volume":"12","author":"Kroe DM","year":"1997","unstructured":"KroeDMKirschCMJensenWA. 1997. 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