Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation.
The macrophage mannose receptor, a pattern recognition molecule and component of innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and likely represents an important clearance mechanism in the lungs of immunocompetent hosts. The purpose of this study was to examine the ability of alveolar macrophages from HIV-infected individuals to bind and phagocytose P. carinii, and to investigate the role of the macrophage mannose receptor in mediating this interaction. Compared with healthy individuals, alveolar macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P = 0.02), primarily reflecting a reduction in the number of organisms associated with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+) counts < 200 cells/mm3 (representing individuals at high clinical risk for P. carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies suggest that HIV infection may alter innate immunity in the lungs, and that impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis of P. carinii may contribute to the susceptibility of HIV-infected individuals to this opportunistic pulmonary pathogen.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. hkoziel@bidmc.harvard.edu
H
H
Koziel
Q
Q
Eichbaum
B A
BA
Kruskal
P
P
Pinkston
R A
RA
Rogers
M Y
MY
Armstrong
F F
FF
Richards
R M
RM
Rose
R A
RA
Ezekowitz
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D018791:CD4 Lymphocyte Count; D002448:Cell Adhesion; D015536:Down-Regulation; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D037181:Lectins, C-Type; D016676:Macrophages, Alveolar / Q000382:microbiology* / Q000502:physiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D010587:Phagocytosis; D011010:Pneumocystis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface