| Accumulation of myeloid-derived suppressor cells in the lungs during Pneumocystis pneumonia. | |
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MedLine Citation:
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PMID: 22868498 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of hematopoietic precursors with the ability to adversely affect host immunity. They have been shown to accumulate in pathological conditions, such as cancer and some microbial diseases. In the mouse and rat models of Pneumocystis pneumonia (PcP), we found a distinct population of cells with MDSC-like morphology in the bronchoalveolar lavage (BAL) fluid, constituting up to 50% of the total cells in BAL fluid. These cells were not seen in the BAL fluid from normal animals or from Pneumocystis-infected animals that had been successfully treated for PcP with a combination of trimethoprim and sulfamethoxazole. With flow cytometry, these cells were found to express the characteristic MDSC surface markers Gr-1 and CD11b in mice or CD11bc and His48 in rats. Using reverse transcription-PCR, we demonstrated that these cells produced high levels of arginase-1 and inducible nitric oxide synthase (iNOS) mRNA. These cells were shown to suppress CD4(+) T-cell proliferation in response to stimulation by anti-CD3 and anti-CD28 antibodies. Adoptive transfer of these cells to normal mice caused lung damage, as indicated by elevated levels of albumin and lactate dehydrogenase in the BAL fluid. These experiments provide evidence of the presence of MDSCs in the lungs during PcP. Further studies on the roles of MDSCs in PcP are warranted in order to develop treatment strategies which can reduce the number of MDSCs and the damage caused by these cells. |
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Authors:
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Chen Zhang; Guang-Sheng Lei; Shoujin Shao; Hsin-Wei Jung; Pamela J Durant; Chao-Hung Lee |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-08-06 |
Journal Detail:
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Title: Infection and immunity Volume: 80 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-09-12 Completed Date: 2012-12-03 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3634-41 Citation Subset: IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Albumins
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metabolism Animals Antigens, CD11b / genetics Bronchoalveolar Lavage Fluid / cytology Cell Proliferation Female Flow Cytometry Gene Expression Regulation / immunology Hematopoietic Stem Cells / cytology*, immunology Immunity, Cellular Lung / cytology* Mice Mice, Inbred C57BL Nitric Oxide Synthase Type II / genetics, metabolism Pneumonia, Pneumocystis / immunology* Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Receptors, Chemokine / genetics, metabolism T-Lymphocytes / cytology, physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI062259/AI/NIAID NIH HHS; R01 HL65170/HL/NHLBI NIH HHS; R03 AI091418/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Albumins; 0/Antigens, CD11b; 0/Gr-1 protein, mouse; 0/Receptors, Chemokine; EC 1.14.13.39/Nitric Oxide Synthase Type II |
| Comments/Corrections | |
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