Category
JFL, Scholars Lounge (380)
Description
Cryptococcus neoformans is an emerging fungal (yeast) pathogen worldwide that causes cryptococcal meningoencephalitis and also responsible for life-threatening diseases of the lungs and skin. In this study, we assessed the production of host immune signals in response to infection with carbon assimilation mutants of C. neoformans to better understand the relationship between pathogen carbon metabolism and virulence. We focused on experimentally creating mutation in pyruvate kinase (pyk1∆), previously shown to have marked deficiencies in virulence without rapid clearance from the host. Cytokine production was investigated both in vivo and ex vivo using cultured macrophages. We furthermore employed additional carbon utilization mutants to illuminate prior findings related to both host clearance and intracellular survival. By examining cytokine production at both the organismal and cellular scale, we hypothesized that alterations in Cryptococcus carbon metabolism may alter the interaction with host immunity leading to measurable changes in immune signaling. These changes in immune signaling may explain the surprising persistence of the severely attenuated pyk1∆ mutant. Previous studies have demonstrated that cells of C. neoformans can survive and replicate within the alveolar macrophages of the lung. Studies show that this ability is accomplished at least in part by modification of the macrophage phagolysosome. Eventually, Cryptococcus can either lyse the host cell or escape without lysis, thereby avoiding a local inflammatory response. This morphological adaptation is crucial for understanding Cryptococcus growth in both immunocompromised and immunocompetent individuals. Defects in glucose utilization result in severely compromised survival within macrophages while showing varied effects on virulence. Understanding the dynamics of this critical pathogen host interactions will provide translational perspectives on potential treatments.
Influence of Pathogen Carbon Metabolism on Host Immunity
JFL, Scholars Lounge (380)
Cryptococcus neoformans is an emerging fungal (yeast) pathogen worldwide that causes cryptococcal meningoencephalitis and also responsible for life-threatening diseases of the lungs and skin. In this study, we assessed the production of host immune signals in response to infection with carbon assimilation mutants of C. neoformans to better understand the relationship between pathogen carbon metabolism and virulence. We focused on experimentally creating mutation in pyruvate kinase (pyk1∆), previously shown to have marked deficiencies in virulence without rapid clearance from the host. Cytokine production was investigated both in vivo and ex vivo using cultured macrophages. We furthermore employed additional carbon utilization mutants to illuminate prior findings related to both host clearance and intracellular survival. By examining cytokine production at both the organismal and cellular scale, we hypothesized that alterations in Cryptococcus carbon metabolism may alter the interaction with host immunity leading to measurable changes in immune signaling. These changes in immune signaling may explain the surprising persistence of the severely attenuated pyk1∆ mutant. Previous studies have demonstrated that cells of C. neoformans can survive and replicate within the alveolar macrophages of the lung. Studies show that this ability is accomplished at least in part by modification of the macrophage phagolysosome. Eventually, Cryptococcus can either lyse the host cell or escape without lysis, thereby avoiding a local inflammatory response. This morphological adaptation is crucial for understanding Cryptococcus growth in both immunocompromised and immunocompetent individuals. Defects in glucose utilization result in severely compromised survival within macrophages while showing varied effects on virulence. Understanding the dynamics of this critical pathogen host interactions will provide translational perspectives on potential treatments.
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