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The Journal of Immunology, 2005, 175: 3244-3251.
Copyright © 2005 by The American Association of Immunologists

An Innate Immune System Cell Is a Major Determinant of Species-Related Susceptibility Differences to Fungal Pneumonia1

Xiuping Shao*, Aron Mednick{dagger}, Mauricio Alvarez{dagger}, Nico van Rooijen§, Arturo Casadevall{dagger},{ddagger} and David L. Goldman2,*

* Department of Pediatrics, {dagger} Department of Microbiology and Immunology, and {ddagger} Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; and § Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, The Netherlands

Rats and mice are considered resistant and susceptible hosts, respectively, for experimental cryptococcosis. For both species, alveolar macrophages (AM) are central components of the host response to pulmonary Cryptococcus neoformans infection. We explored the role of AM in three strains of mice and three strains of rats during cryptococcal infection by comparing the outcome of infection after macrophage depletion using liposomal clodronate. AM depletion was associated with enhancement and amelioration of disease in rats and mice, respectively, as measured by lung fungal burden. The apparent protective role for AM in rats correlated with enhanced anticryptococcal activity as measured by phagocytic activity, oxidative burst, lysozyme secretion, and ability to limit intracellular growth of C. neoformans. Furthermore, rat AM were more resistant to lysis in association with intracellular infection. In summary, differences in AM function in rats and mice suggest an explanation for the species differences in susceptibility to C. neoformans based on the inherent efficacy of a central effector cell of the innate immune system.




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