Elucidating the pathogenesis of spores from the human fungal pathogen Cryptococcus neoformans.
Cryptococcus neoformans was first described as a human fungal pathogen more than a century ago. One aspect of the C. neoformans infectious life cycle that has been the subject of earnest debate is whether the spores are pathogenic. Despite much speculation, no direct evidence has been presented to resolve this outstanding question. We present evidence that C. neoformans spores are pathogenic in a mouse intranasal inhalation model of infection. In addition, we provide mechanistic insights into spore-host interactions. We found that C. neoformans spores were phagocytosed by alveolar macrophages via interactions between fungal beta-(1,3)-glucan and the host receptors Dectin-1 and CD11b. Moreover, we discovered an important link between spore survival and macrophage activation state: intracellular spores were susceptible to reactive oxygen-nitrogen species. We anticipate these results will serve as the basis for a model to further investigate the pathogenic implications of infections caused by fungal spores.
Giles
Steven S
SS
Department of Biomolecular Chemistry, University of Wisconsin-Madison, USA.
Dagenais
Taylor R T
TR
Botts
Michael R
MR
Keller
Nancy P
NP
Hull
Christina M
CM
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D005260:Female; D054884:Host-Pathogen Interactions; D037181:Lectins, C-Type; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000276:immunology; D010587:Phagocytosis; D011485:Protein Binding; D013172:Spores, Fungal / Q000472:pathogenicity*; D047071:beta-Glucans / Q000378:metabolism; D000099181:Dectin-1
D039481:CD11b Antigen; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D047071:beta-Glucans; D000099181:Dectin-1; C033363:beta-1,3-glucan