{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:40:45Z","timestamp":1790887245035,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The immune response protects against Pneumocystis infection but is also a key component of Pneumocystis pneumonia (PcP)\u2013related immunopathogenesis. Signaling through myeloid differentiation factor 88 (MyD88) is critical for activation of immune pathways downstream of TLRs and IL-1R. To determine whether MyD88 regulates normal host defense against Pneumocystis, nonimmunosuppressed wild-type (WT) and MyD88-deficient mice were infected. MyD88\u2212\/\u2212 mice had higher early Pneumocystis burdens than did WT mice but mounted an effective adaptive immune response and cleared Pneumocystis similarly to WT. However, MyD88\u2212\/\u2212 mice displayed a more intense and prolonged pulmonary immune response than did WT mice. To determine the role of MyD88 in the development of PcP-related immunopathogenesis, WT and MyD88\u2212\/\u2212 mice were rendered susceptible to PcP by depletion of CD4+ T cells. At 4 wk postinfection, CD4-depleted WT and MyD88\u2212\/\u2212 mice harbored similar organism burdens, but MyD88\u2212\/\u2212 mice were protected from the PcP-related respiratory impairment observed in WT mice. Improved pulmonary physiology in MyD88\u2212\/\u2212 mice correlated with lower lung CCL2 levels and reduced cell recruitment. However, by 5 wk postinfection, the overall health of MyD88\u2212\/\u2212 mice began to deteriorate rapidly relative to WT, with accelerated weight loss, impaired lung function, and exacerbated alveolar inflammation. This physiological decline of MyD88\u2212\/\u2212 mice was associated with increased TNF-\u03b1 and IFN-\u03b3 in the lung, and by the inability to control Pneumocystis burden. Thus, MyD88 is not required for resistance to Pneumocystis infection, but limits the adaptive immune response in immunocompetent mice. In the setting of active PcP, MyD88 signaling contributes to both immunopathogenesis and control of fungal burden.<\/jats:p>","DOI":"10.4049\/jimmunol.1301431","type":"journal-article","created":{"date-parts":[[2013,11,30]],"date-time":"2013-11-30T01:41:55Z","timestamp":1385775715000},"page":"282-292","source":"Crossref","is-referenced-by-count":14,"title":["MyD88 Signaling Regulates Both Host Defense and Immunopathogenesis during <i>Pneumocystis<\/i> Infection"],"prefix":"10.1093","volume":"192","author":[{"given":"Sheila N","family":"Bello-Irizarry","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J","family":"Johnston","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Gigliotti","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry W","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Division of Infectious Diseases, Department of Pediatrics, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2025032404062363600_r1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1399-3062.2012.00740.x","article-title":"Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past","volume":"14","author":"Wang","year":"2012","journal-title":"Transpl. 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