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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0803398v1 183/4/2678    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Serbina, N. V. Articles by Pamer, E. G. PubMed PubMed Citation Articles by Serbina, N. V. Articles by Pamer, E. G.

Distinct Responses of Human Monocyte Subsets to Aspergillus fumigatus Conidia¹

Natalya V. Serbina^2,*, Mathew Cherny^*, Chao Shi^*, Sharon A. Bleau, Nancy H. Collins, James W. Young and Eric G. Pamer^*

^* Infectious Disease Service, Department of Medicine; Department of Clinical Laboratories, and Allogeneic Bone Marrow Transplant Service and Laboratory of Cellular Immunology, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

Aspergillus fumigatus is an environmental fungus that causes life-threatening infections in neutropenic patients. In the absence of intact innate immunity, inhaled A. fumigatus spores (conidia) germinate in the lung, forming hyphae that invade blood vessels and disseminate to other tissues. Although macrophages and neutrophils are postulated to provide defense against invasive fungal infection, animal models and human studies suggest that circulating monocytes also contribute to antifungal immunity. Although human monocyte subsets, defined as either CD14⁺CD16^– or CD14⁺CD16⁺, have been extensively characterized, their respective roles during fungal infection remain undefined. We isolated CD14⁺CD16^– and CD14⁺CD16⁺ monocytes from healthy allogeneic hematopoietic stem cell transplantation donors and compared their ability to phagocytose and inhibit A. fumigatus conidia. Both monocyte subsets efficiently phagocytose conidia, but only CD14⁺CD16^– monocytes inhibit conidial germination yet secrete little TNF. In contrast CD14⁺CD16⁺ do not inhibit conidial germination and secrete large amounts of TNF. Although CD14⁺CD16^– and CD14⁺CD16⁺ monocytes differ in their response to dormant conidia, responses are similar if conidia are already germinated at the time of monocyte uptake. Our study demonstrates that functional CD14⁺CD16^– and CD14⁺CD16⁺ monocytes can be isolated from allogeneic hematopoietic stem cell transplantation donors and that these subsets differ in their response to A. fumigatus conidia.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Institutes of Health (K12 CA120121 to N.V.S.; AI67359 and AI39031 to E.G.P., M.C., and C.S.; CA23766 to E.G.P. and J.W.Y.).

² Address correspondence and reprint requests to Dr. Natalya V. Serbina, Infectious Diseases Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. E-mail address: serbinan{at}mskcc.org

³ Abbreviations used in this paper: allo-HSCT, allogeneic hematopoietic stem cell transplantation; HKLM, heat killed Listeria monocytogenes; PAP, pulmonary alveolar proteinosis.

⁴ The online version of this article contains supplemental material.