Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 198, Issue 11, Pages 1677-1688Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030932
Keywords
lung; leukocyte; innate; yeast; chemokine
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL062052] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL62052, HL61721, R01 HL062052] Funding Source: Medline
- Wellcome Trust [055109] Funding Source: Medline
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Innate immune mechanisms against Pneumocystis carinii, a frequent cause of pneumonia in immuno-compromised individuals, are not well understood. Using both real time polymerase chain reaction as a measure of organism viability and fluorescent deconvolution microscopy, we show that nonopsonic phagocytosis of P. carinii by alveolar macrophages is mediated by the Dectin-1 beta-glucan receptor and that the subsequent generation of hydrogen peroxide is involved in alveolar macrophage-mediated killing of P. carinii. The macrophage Dectin-1 beta-glucan receptor colocalized with the P. carinii cyst wall. However, blockage of Dectin-1 with high concentrations of anti-Dectin-1 antibody inhibited binding and concomitant killing of P. carinii by alveolar macrophages. Furthermore, RAW 264.7 macrophages overexpressing Dectin-1 bound P. carinii at a higher level than control RAW cells. In the presence of Dectin-1 blockage, killing of opsonized P. carinii could be restored through FcgammaRII/III receptors. Opsonized P. carinii could also be efficiently killed in the presence of FcgammaRII/III receptor blockage through Dectin-1-mediated phagocytosis. We further show that Dectin-1 is required for P. carinii-induced macrophage inflammatory protein 2 production by alveolar macrophages. Taken together, these results show that nonopsonic phagocytosis and subsequent killing of P. carinii by alveolar macrophages is dependent upon recognition by the Dectin-1 P-glucan receptor.
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