| Title: | The RGS protein Crg2 is required for establishment and progression of murine pulmonary cryptococcosis |
| Address: | "Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA" |
| DOI: | 10.3109/13693786.2010.512618 |
| ISSN/ISBN: | 1460-2709 (Electronic) 1369-3786 (Print) 1369-3786 (Linking) |
| Abstract: | "Cryptococcal regulators of G protein signaling (CRG) are important for growth, differentiation, and virulence of Cryptococcus neoformans. Disruption of CRG2 resulted in dysregulated cAMP signaling and attenuated virulence, whereas disruption of CRG1 increased pheromone responses and enhanced virulence in the archetypal H99 strain. In tests with newly constructed near congenic mutants, a distinction between crg2Delta and crg1Delta gene expression was not apparent during macrophage interaction. Intranasal inoculation indicated that crg2Delta, crg1Delta, and wild-type strains reached the lungs within 0.5 hours of infection. However, CFUs were significantly decreased for crg2Delta at 2, 7, and 14 days post-infection. In contrast, crg1Delta proliferated to the same extent as the wild type (WT). Lung edema was not apparent in mice infected with crg2Delta 0.5 hours post-infection, which showed little cellular infiltrate in comparison to WT. Alveolar septal thickening was most evident in mice infected with crg1Delta, while mice infected with WT exhibited decreased septal thickening at later time points. Consistent with these observations, crg2Delta was less efficient in the elicitation of Th2 immune responses in a multiplex cytokine assay. Our results suggest that Crg2 is critical for establishment of early pulmonary infection and for persistence of infection, Crg1 regulates virulence in a strain-specific manner, and crg2Delta, crg1Delta and WT can all be distinguished on the basis of host tissue responses" |
| Keywords: | "Animals Colony Count, Microbial Cryptococcosis/*microbiology/pathology Cryptococcus neoformans/*pathogenicity Female Fungal Proteins/genetics/*metabolism Gene Deletion Lung/microbiology/pathology Lung Diseases, Fungal/*microbiology/pathology Mice RGS Prot;" |
| Notes: | "MedlineWhittington, Amy Wang, Ping eng AI074001/AI/NIAID NIH HHS/ AI054958/AI/NIAID NIH HHS/ R56 AI074001/AI/NIAID NIH HHS/ R01 AI054958/AI/NIAID NIH HHS/ R01 AI074001/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2010/09/08 Med Mycol. 2011 Apr; 49(3):263-75. doi: 10.3109/13693786.2010.512618. Epub 2010 Sep 6" |
