Pulmonary cryptococcosis induces chitinase in the rat

Alfin G Vicencio,Swati Narain,James Ritch,Zhongfang Du,Wang Yong Zeng,David L Goldman,Arturo Casadevall

doi:10.1186/1465-9921-9-40

Alfin G Vicencio, Swati Narain + Show 5 more

Open Access

https://doi.org/10.1186/1465-9921-9-40

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Abstract

BackgroundWe previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Because the cell wall of C. neoformans consists of chitin, and since acidic mammalian chitinase (AMCase) has recently been implicated as a novel mediator of asthma, we sought to determine whether such infection induces chitinase activity and expression of AMCase in the rat.MethodsWe utilized a previously-established model of chronic C. neoformans pulmonary infection in the rat to analyze the activity, expression and localization of AMCase.ResultsOur studies indicate that intratracheal inoculation of C. neoformans induces chitinase activity within the lung and bronchoalveolar lavage fluid of infected rats. Chitinase activity is also elicited by pulmonary infection with other fungi (e.g. C. albicans), but not by the inoculation of dead organisms. Enhanced chitinase activity reflects increased AMCase expression by airway epithelial cells and alveolar macrophages. Systemic cryptococcosis is not associated with increased pulmonary chitinase activity or AMCase expression.ConclusionOur findings indicate a possible link between respiratory fungal infections, including C. neoformans, and asthma through the induction of AMCase.

Highlights

We previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model
Fungal burden All rats inoculated with C. neoformans and C. albicans were actively infected at the time of chitinase determinations
Western blot analysis and densitometry of BAL fluid (BALF) demonstrated that acidic mammalian chitinase (AMCase) expression parallels general chitinase activity

Summary

Introduction

We previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Asthma is the most common chronic illness in childhood, and rates of disease are highest in urban areas including the Bronx. Previous studies from our laboratory demonstrate that sub-clinical pulmonary infection with Cryptococcus neoformans, a fungus present in high concentrations in pigeon guano, induces increased airway reactivity in a rat model [3]. We have demonstrated that sub-clinical C. neoformans infection is common among Bronx children, a cohort with an extraordinarily high rate of asthma, suggesting a potential role for this type of infection in asthma pathogenesis [4]. The mechanisms by which chronic infection by C. neoformans and other fungal organisms could lead to asthma are unknown.

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