Host immune defense against Aspergillus fumigatus : insight from experimental systemic (disseminated) infection
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IMMUNOLOGY IN SERBIA
Host immune defense against Aspergillus fumigatus: insight from experimental systemic (disseminated) infection I. Mirkov • S. Stosic-Grujicic • M. Kataranovski
Published online: 3 March 2012 Ó Springer Science+Business Media, LLC 2012
M. Kataranovski
Abstract Model of systemic Aspergillus fumigatus infection induced by intravenous application of conidia is suitable for studying important aspects of invasive aspergillosis including relationship between infection and mortality, dissemination of infection and immune mechanisms involved in host resistance to this fungus. Use of this model allows the investigation of both innate and adaptive immune response characteristics in resistant/susceptible host, and investigating the contribution of genetic background and cytokine gene deficiency improves the knowledge of the diversity of mechanisms of immune response to Aspergillus infection. Studying of various aspects of systemic aspergillosis contributes to development of antifungal drugs. Keywords
Aspergillus fumigatus Systemic infection Spleen immune response Tissue immune responses
Introduction Animal models of diseases caused by opportunistic fungus Aspergillus fumigatus (A. fumigatus) greatly improved our knowledge of pathogenesis of aspergillosis, disease transmission, as well as defensive mechanisms of the host [1–3]. Murine models of aspergillosis are most often used to explore mechanisms of pathogenesis of disease and antifungal immune defense mechanisms in the four major forms of aspergillosis: bronchopulmonary aspergillosis, invasive pulmonary aspergillosis, systemic (disseminated) aspergillosis, and infection of central nervous system [1, 4]. I. Mirkov M. Kataranovski (&) Department of Ecology, Institute for Biological Research ‘‘Sinisa Stankovic’’, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia e-mail: [email protected] S. Stosic-Grujicic Department of Immunology, Institute for Biological Research ‘‘Sinisa Stankovic’’, University of Belgrade, Belgrade, Serbia M. Kataranovski Faculty of Biology, Institute of Physiology and Biochemistry, University of Belgrade, Belgrade, Serbia
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A. fumigatus infection via pulmonary routes is usually induced in animals subjected to immunosuppressants (glucocorticoids or cyclophosphamide), but these treatments affect the characteristics of the immune response both before as well as during infection [5, 6]. Systemic aspergillosis induced by intravenous (i.v.) conidia administration can, however, be established in immunocompetent animals, and exogenous immune suppression is seldom employed [7–9]. Although i.v. fungal administration is not a natural route of infection in humans, model of systemic aspergillosis in immunocompetent animals makes possible investigations of mechanisms of resistance to Aspergillus in the absence of confounding factors. This model proved particularly suitable for studying relationship between infection and mortality and dissemination of infection, which are important aspects of invasive as
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