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Infection and Immunity, December 2007, p. 5663-5668, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.01542-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of Neutrophils in Preventing and Resolving Acute Fungal Sinusitis ^,

Division of Pulmonary and Critical Care Medicine,¹ Departments of Internal Medicine and of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan,² Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan³

Received 25 September 2006/ Returned for modification 3 November 2006/ Accepted 31 August 2007

Acute fungal sinusitis (AFS) is a devastating disease of the paranasal sinuses afflicting immunocompromised individuals. Knowledge about this disease is limited to clinical observations because there are no animal models in which to study the pathogenesis of the infection. Our goal was to develop a murine model of AFS and examine the role of neutrophils in host defense within the nasal cavity. Female C57BL/6 mice were depleted of neutrophils using anti-Gr-1 monoclonal antibody from day –1 to day 5 postinfection to initiate a transient neutropenia within the mice. At day 0, Aspergillus fumigatus conidia were administered intranasally. The untreated Aspergillus-exposed group had significant neutrophil recruitment by day 3, but by day 7 the leukocyte numbers had returned to unexposed levels. There was not a significant influx of mononuclear cells at either time point. In contrast, beginning at day 3 postinfection and continuing through day 7, anti-Gr-1-treated mice had increased cellular recruitment consisting of banded neutrophils at day 3 and mature neutrophils at day 7. Hyphal masses developed only in the anti-Gr-1-treated mice (25 to 36%) but only during the period of treatment. When the treatment was discontinued, hyphal masses could no longer be detected in the nasal cavities of these mice. In contrast, cyclophosphamide treatment did not induce neutropenia, and the nasal cavity remained free of hyphal masses. These studies demonstrate the feasibility of using this model to study AFS and implicate neutrophils in protection of the sinuses against acute Aspergillus infection and in clearance of established hyphal masses.

Published ahead of print on 17 September 2007.

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Editor: A. Casadevall