{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:04:18Z","timestamp":1791097458973,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The opportunistic organism Pneumocystis carinii (Pc) produces a life-threatening pneumonia (PcP) in patients with low CD4+ T cell counts. Animal models of HIV-AIDS-related PcP indicate that development of severe disease is dependent on the presence of CD8+ T cells and the TNF receptors (TNFR) TNFRsf1a and TNFRsf1b. To distinguish roles of parenchymal and hematopoietic cell TNF signaling in PcP-related lung injury, murine bone marrow transplant chimeras of wild-type, C57BL6\/J, and TNFRsf1a\/1b double-null origin were generated, CD4+ T cell depleted, and inoculated with Pc. As expected, C57 \u2192 C57 chimeras (donor marrow \u2192 recipient) developed significant disease as assessed by weight loss, impaired pulmonary function (lung resistance and dynamic lung compliance), and inflammatory cell infiltration. In contrast, TNFRsf1a\/1b\u2212\/\u2212 \u2192 TNFRsf1a\/1b\u2212\/\u2212 mice were relatively mildly affected despite carrying the greatest organism burden. Mice solely lacking parenchymal TNFRs (C57 \u2192 TNFRsf1a\/1b\u2212\/\u2212) had milder disease than did C57 \u2192 C57 mice. Both groups of mice with TNFR-deficient parenchymal cells had low bronchoalveolar lavage fluid total cell counts and fewer lavageable CD8+ T cells than did C57 \u2192 C57 mice, suggesting that parenchymal TNFR signaling contributes to PcP-related immunopathology through the recruitment of damaging immune cells. Interestingly, mice with wild-type parenchymal cells but TNFRsf1a\/1b\u2212\/\u2212 hematopoietic cells (TNFRsf1a\/1b\u2212\/\u2212 \u2192 C57) displayed exacerbated disease characterized by increased MCP-1 and KC production in the lung and increased macrophage and lymphocyte numbers in the lavage, indicating a dysregulated immune response. This study supports a key role of parenchymal cell TNFRs in lung injury induced by Pc and a potential protective effect of receptors on radiosensitive, bone marrow-derived cells.<\/jats:p>","DOI":"10.4049\/jimmunol.181.2.1409","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:27:05Z","timestamp":1397849225000},"page":"1409-1419","source":"Crossref","is-referenced-by-count":19,"title":["Parenchymal Cell TNF Receptors Contribute to Inflammatory Cell Recruitment and Respiratory Failure in\n                    <i>Pneumocystis carinii<\/i>\n                    -Induced Pneumonia"],"prefix":"10.1093","volume":"181","author":[{"given":"Gloria S","family":"Pryhuber","sequence":"first","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Environmental Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidie L","family":"Huyck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Bhagwat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Environmental Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob N","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Environmental Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Gigliotti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry W","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,7,15]]},"reference":[{"key":"2026012807083379700_R1","first-page":"23","article-title":"Pneumocystis infections: the iceberg?","volume-title":"Med. 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