Early neutrophil recruitment and aggregation in the murine lung inhibit germination of Aspergillus fumigatus conidia

Author:

Bonnett CR, Cornish EJ, Harmsen AG, Burritt JB.

Date: 2 October 2006

Abstract:

Several types of polymorphonuclear neutrophil (PMN) deficiency predispose to fatal Aspergillus fumigatus infection. In order to study the defensive role of PMN in the lungs, with particular reference to PMN recruitment and antimicrobial oxidant activity, responses to pulmonary instillation of A. fumigatus conidia were examined. Responses were compared in BALB/c and C57Bl/6 mice with those in CXCR2(-/-) and gp91(phox)(-/-) 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, PMN were recruited to the lungs and formed oxidase-active aggregates with conidia which inhibited germination. In C57Bl/6, gp91(phox)(-/-) and CXCR2(-/-) mice, PMN recruitment was slower and there was increased germination compared to BALB/c mice at 6 and 12 h. In gp91(phox)(-/-) mice, germination in PMN aggregates was extensive, but negligible in alveolar macrophages (AM). Lungs sections taken 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 gp91(phox)(-/-) 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

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