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We observed enhanced pulmonary M1 macrophage polarization in immunosuppressed (IS) hosts, but an M2 predominant response in immunocompetent (IC) hosts following<jats:named-content content-type=\"genus-species\">Pneumocystis carinii<\/jats:named-content>challenge. Increased inflammation and inducible nitric oxide synthase (iNOS) levels characterized the M1 response. However, macrophage ability to produce nitric oxide was defective. In contrast, the lungs of IC animals revealed a prominent M2 gene signature, and these macrophages effectively elicited an oxidative burst associated with clearance of<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>. In addition, during<jats:named-content content-type=\"genus-species\">P. carinii<\/jats:named-content>infection the expression of Dectin-1, a critical receptor for recognition and clearance of<jats:named-content content-type=\"genus-species\">P. carinii<\/jats:named-content>, was upregulated in macrophages of IC animals but suppressed in IS animals. In the absence of an appropriate cytokine milieu for M2 differentiation,<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>induced an M1 response both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. The M1 response induced by<jats:named-content content-type=\"genus-species\">P. carinii<\/jats:named-content>was plastic in nature and reversible with appropriate cytokine stimuli. Finally, we tested whether macrophage polarization can be modulated<jats:italic>in vivo<\/jats:italic>and used to help manage the pathogenesis of<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>pneumonia by adoptive transfer. Treatment with both M1 and M2 cells significantly improved survival of<jats:named-content content-type=\"genus-species\">P. carinii<\/jats:named-content>-infected IS hosts. However, M2 treatment provided the best outcomes with efficient clearance of<jats:named-content content-type=\"genus-species\">P. carinii<\/jats:named-content>and reduced inflammation.<\/jats:p>","DOI":"10.1128\/iai.00939-16","type":"journal-article","created":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T18:06:47Z","timestamp":1482516407000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Differential Macrophage Polarization from Pneumocystis in Immunocompetent and Immunosuppressed Hosts: Potential Adjunctive Therapy during Pneumonia"],"prefix":"10.1128","volume":"85","author":[{"given":"Vijayalakshmi","family":"Nandakumar","sequence":"first","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanne","family":"Hebrink","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Jenson","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Kottom","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Limper","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA"},{"name":"Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.201009-062WR"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.5.1204"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3600"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1937"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59643"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.008"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.65"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.323"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00107-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1451"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400318"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.052"},{"key":"e_1_3_3_16_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4049\/jimmunol.156.2.523","article-title":"Selective activation-induced apoptosis of peripheral T cells imposed by macrophages: a potential mechanism of antigen-specific peripheral lymphocyte deletion","volume":"156","author":"Munn DH","year":"1996","unstructured":"Munn DH Pressey J Beall AC Hudes R Alderson MR . 1996. 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