title: An innate immune system cell is a major determinant of species-related susceptibility differences to fungal pneumonia.
abstract: 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 anti-cryptococcal 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.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Shao
authors.forename: Aron
authors.initials: A
authors.lastname: Mednick
authors.forename: Mauricio
authors.initials: M
authors.lastname: Alvarez
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: David L
authors.initials: DL
authors.lastname: Goldman
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000254:growth & development; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D008172:Lung Diseases, Fungal / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D011014:Pneumonia / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst; D013045:Species Specificity
chemical_list: D016207:Cytokines; D009569:Nitric Oxide; D009113:Muramidase