Surfactant protein D enhances Pneumocystis infection in immune-suppressed mice.
To further determine the role of surfactant protein (SP)-D in the pathogenesis of Pneumocystis pneumonia, a mouse model of transgenic overexpression (OE) of SP-D was studied. These animals produce roughly 30- to 50-fold greater SP-D than their wild-type (WT) counterparts but show no other differences in lung morphology and function. Animals in both the SP-D OE and WT groups were depleted of CD4 lymphocytes with weekly injections of GK1.5 antibody, before Pneumocystis inoculation, and throughout the subsequent infection period. At various time points, mice were killed and analyzed for inflammatory parameters and organism burden. Proinflammatory cytokines in bronchoalveolar lavage fluid were elevated throughout the period of infection, with OE animals exhibiting significantly higher levels of TNF-alpha and macrophage inflammatory protein-2 compared with WT controls. The total number of cells in the lavage fluid was also increased significantly only in the OE group, whereas the cell differential composition demonstrated lymphocyte and eosinophil infiltration in both groups of animals. Significantly, the organism burden was markedly higher in the SP-D OE animals, whereas the WT mice demonstrated little alteration in organism number over the course of infection. These results further indicate that SP-D facilitates the development of Pneumocystis infection and related lung inflammation in an immunosuppressed mouse model.
Vuk-Pavlovic
Zvezdana
Z
Thoracic Diseases Research Unit, Division of Pulmonary, Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Mo
Eun K
EK
Icenhour
Crystal R
CR
Standing
Joseph E
JE
Fisher
James H
JH
Limper
Andrew H
AH
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D054426:Chemokine CXCL2; D004804:Eosinophils / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008212:Lymphocyte Depletion; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D015846:Monokines / Q000378:metabolism; D011010:Pneumocystis / Q000502:physiology*; D016720:Pneumocystis Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D015846:Monokines; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha