title: Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
abstract: We examined gene expression levels of multiple chemokines and chemokine receptors during Pneumocystis murina infection in wild-type and immunosuppressed mice, using microarrays and qPCR. In wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, Cxcr6, and Cxcr2 increased at days 32-41 post-infection, with a return to baseline by day 75-150. Concomitant increases were seen in Ccr2, Cxcr3, and Cxcr6, but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2, Cxcr3, and Cxcr6 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Bishop
authors.affiliation: Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Sassi
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
authors.affiliation: Laboratory of Immunopathogenesis and Bioinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Laboratory of Immunopathogenesis and Bioinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Da Wei
authors.initials: da W
authors.lastname: Huang
authors.affiliation: Laboratory of Immunopathogenesis and Bioinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Sherman
authors.affiliation: Laboratory of Immunopathogenesis and Bioinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Laboratory of Immunopathogenesis and Bioinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Immunopathogenesis and Bioinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jkovacs@mail.nih.gov.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018925:Chemokines / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011010:Pneumocystis / Q000276:immunology*; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine
keywords: Chemokine receptor; Chemokines; Knock-out mice; PCP; Pneumocystis