The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published 1 December 2003. doi:10.1084/jem.20030932
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© Rockefeller University Press, 0022-1007/2003/12/1677 $5.00
The Journal of Experimental Medicine, Volume 198, Number 11, 1677-1688

Alveolar Macrophage–mediated Killing of Pneumocystis carinii f. sp. muris Involves Molecular Recognition by the Dectin-1 ß-Glucan Receptor

Chad Steele1, Luis Marrero2, Steve Swain3, Allen G. Harmsen3, Mingquan Zheng1, Gordon D. Brown4, Siamon Gordon4, Judd E. Shellito2 and Jay K. Kolls1

1 Department of Pediatrics, Division of Pulmonology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
2 Section of Pulmonary and Critical Care, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112
3 Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717
4 Sir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom

Address correspondence to Jay K. Kolls, Department of Pediatrics, Division of Pulmonology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Suite 3765, 3705 Fifth Avenue, Pittsburgh, PA 15213. Phone: (412) 692-5630; Fax: (412) 692-6645; email: jay.kolls{at}chp.edu

Innate immune mechanisms against Pneumocystis carinii, a frequent cause of pneumonia in immunocompromised 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 ß-glucan receptor and that the subsequent generation of hydrogen peroxide is involved in alveolar macrophage–mediated killing of P. carinii. The macrophage Dectin-1 ß-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 Fc{gamma}RII/III receptors. Opsonized P. carinii could also be efficiently killed in the presence of Fc{gamma}RII/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 ß-glucan receptor.

Key Words: lung • leukocyte • innate • yeast • chemokine

Abbreviations used in this paper: MIP, macrophage inflammatory protein; MnTMPyP, manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride; MR, mannose receptor.


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