{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:17:02Z","timestamp":1790371022683,"version":"4.1.0"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"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":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>pneumonia was first diagnosed in malnourished children and has more recently been found in children with upper respiratory symptoms. We previously reported that there is a significant delay in the immune response in newborn mice infected with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>compared to adults (Garvy BA, Harmsen AG, Infect. Immun. 64:3987\u20133992, 1996, and Garvy BA, Qureshi M, J. Immunol. 165:6480\u20136486, 2000). This delay is characterized by the failure of neonatal lungs to upregulate proinflammatory cytokines and attract T cells into the alveoli. Here, we report that regardless of the age at which we infected the mice, they failed to mount an inflammatory response in the alveolar spaces until they were 21 days of age or older. Anti-inflammatory cytokines had some role in dampening inflammation, since interleukin-10 (IL-10)-deficient pups cleared<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>faster than wild-type pups and the neutralization of transforming growth factor beta (TGF-\u03b2) with specific antibody enhanced T cell migration into the lungs at later time points. However, the clearance kinetics were similar to those of control pups, suggesting that there is an intrinsic deficiency in the ability of innate immunity to control<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>. We found, using an adoptive transfer strategy, that the lung environment contributes to association of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>organisms with alveolar macrophages, implying no intrinsic deficiency in the binding of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>by neonatal macrophages. Using both<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>assays, we found that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>organisms were less able to stimulate translocation of NF-\u03baB to the nucleus of alveolar macrophages from neonatal mice. These data indicate that there is an early unresponsiveness of neonatal alveolar macrophages to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pneumocystis<\/jats:named-content>infection that is both intrinsic and related to the immunosuppressive environment found in neonatal lungs.<\/jats:p>","DOI":"10.1128\/iai.05707-11","type":"journal-article","created":{"date-parts":[[2012,6,5]],"date-time":"2012-06-05T10:08:47Z","timestamp":1338890927000},"page":"2835-2846","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Alveolar Macrophages in Neonatal Mice Are Inherently Unresponsive to Pneumocystis murina Infection"],"prefix":"10.1128","volume":"80","author":[{"given":"Cathryn","family":"Kurkjian","sequence":"first","affiliation":[{"name":"Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Hollifield","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA"},{"name":"Veteran's Administration Medical Center, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Louise","family":"Lines","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Rogosky","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry M.","family":"Empey","sequence":"additional","affiliation":[{"name":"Clinical Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA"},{"name":"Internal Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Veteran's Administration Medical Center, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Garvy","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA"},{"name":"Internal Medicine, University of Kentucky, Lexington, Kentucky, USA"},{"name":"Veteran's Administration Medical Center, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1394"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21403"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.11.3859-3862.1991"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/5.2.186"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.103.2_Supplement.116S-a"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1497"},{"key":"e_1_3_3_8_2","volume-title":"Lung development.","author":"Bourbon JR","year":"1999","unstructured":"BourbonJR. 1999. 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