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Infection and Immunity, December 2006, p. 6528-6539, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.00909-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Early Neutrophil Recruitment and Aggregation in the Murine Lung Inhibit Germination of Aspergillus fumigatus Conidia{triangledown}

Colin R. Bonnett,1,{dagger} E. Jean Cornish,1 Allen G. Harmsen,2 and James B. Burritt1*

Departments of Microbiology,1 Veterinary Molecular Biology, Montana State University, Bozeman, Montana 597172

Received 7 June 2006/ Returned for modification 1 July 2006/ Accepted 7 August 2006

Several types of polymorphonuclear neutrophil (PMN) deficiency are a predisposing condition for fatal Aspergillus fumigatus infection. In order to study the defensive role of PMNs in the lungs, with particular reference to PMN recruitment and antimicrobial oxidant activity, responses to pulmonary instillation of A. fumigatus conidia were examined. Responses in BALB/c and C57BL/6 mice were compared with those in CXCR2–/– and gp91phox–/– mice, which are known to have delayed recruitment of PMN to the lungs in response to inflammatory stimuli and inactive NADPH oxidase, respectively. In BALB/c mice, PMNs were recruited to the lungs and formed oxidase-active aggregates with conidia, which inhibited germination. In C57BL/6, gp91phox–/–, and CXCR2–/– mice, PMN recruitment was slower and there was increased germination compared to that in BALB/c mice at 6 and 12 h. In gp91phox–/– mice, germination was extensive in PMN aggregates but negligible in alveolar macrophages (AM). Lung sections taken at 6 and 48 h from BALB/c mice showed PMN accumulation at peribronchiolar sites but no germinating conidia. Those from C57BL/6 and CXCR2–/– mice showed germinating conidia at 6 h but not at 48 h and few inflammatory cells. In contrast, those from gp91phox–/– mice showed germination at 6 h with more-extensive hyphal proliferation and tissue invasion at 48 h. These results indicate that when the lungs are exposed to large numbers of conidia, in addition to the phagocytic activity of AM, early PMN recruitment and formation of oxidative-active aggregates are essential in preventing germination of A. fumigatus conidia.

* Corresponding author. Mailing address: 109 Lewis Hall, Department of Microbiology, Montana State University, Bozeman, MT 59717. Phone: (406) 994-5667. Fax: (406) 994-4926. E-mail: jburritt{at}montana.edu.

{triangledown} Published ahead of print on 18 August 2006.

Editor: A. Casadevall

{dagger} Present address: College of Veterinary Medicine, Washington State University, PO Box 647012, Pullman, WA 99164-7012.

Infection and Immunity, December 2006, p. 6528-6539, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.00909-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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