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Infect. Immun. doi:10.1128/IAI.01542-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of the Role of Neutrophils in Preventing and Resolving Acute Fungal Sinusitis

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

^* To whom correspondence should be addressed. Email: ghuff{at}umich.edu.

	Abstract

Acute Fungal Sinusitis (AFS) is a devastating disease of the paranasal sinuses afflicting immunocompromised individuals. Knowledge about the 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 address the role of neutrophils in host defense within the nasal cavity. Female C57BL/6 mice were depleted of neutrophils using anti-Gr-1 mAb from days -1 to day 5 post-infection to initiate a transient neutropenia within the mice. At day 0, A. fumigatus conidia were administered intranasally. The untreated Aspergillus-exposed group had significant neutrophil recruitment by day 3, but by day 7 the leukocyte numbers returned to unexposed levels. There was not a significant influx of mononuclear cells at either timepoint. In contrast, beginning at day 3 post-infection 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 (25-36%) 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 nasasl cavity remained free of hyphal masses. These studies demonstrate the feasibility of this model to study AFS and implicate neutrophils in protection of the sinuses from acute Aspergillus infection and in clearance of established hyphal masses.