Dendritic cell-associated C-type lectin 1 (Dectin-1, also known as CLEC7A) is an innate immune pattern recognition receptor that recognizes β-glucan on the Candida albicans cell wall. Recognition of β-glucan by immune cells leads to phagocytosis, oxidative burst, cytokine and chemokine production. We looked for specific mechanisms that coordinate phagocytosis downstream of Dectin-1 leading to actin reorganization and internalization of fungus. We found that stimulation of Dectin-1 by soluble β-glucan leads to mechanical force generation and areal contraction in Dectin-1-transfected HEK-293 cells and M1 macrophages. With inhibitor studies, we found this force generation is a spleen tyrosine kinase (SYK)-independent, but SRC family kinase (SFK)-dependent process mediated through the RHOA-ROCK-myosin light chain (MLC) pathway. We confirmed activation of RHOA downstream of Dectin-1 using activity assays and stress fiber formation. Through phagocytosis assays, we found direct evidence for the importance of RHOA-ROCK-MLC signaling in the process of phagocytosis of C. albicans.
Dectin-1 is an innate immune pattern recognition receptor which recognizes β-glucan on the Candida albicans (C. albicans) cell wall. Recognition of β-glucan by immune cells leads to phagocytosis, oxidative burst, cytokine and chemokine production. We looked for specific mechanisms that coordinate phagocytosis downstream of Dectin-1 leading to actin reorganization and internalization of fungus. We found that stimulation of Dectin-1 by soluble b-glucan leads to mechanical force generation and areal contraction in Dectin-1 transfected HEK-293 cells and M1 macrophages. With inhibitor studies, we found this force generation is a SYK-independent, SFK (SRC Family Kinase)-dependent process mediated through the RHOA-ROCK-MLC pathway. We confirmed activation of RHOA downstream of Dectin-1 using G-LISA and stress fiber formation. Through phagocytosis assays, we found direct evidence for importance of RHOA-ROCK-MLC pathway in process of phagocytosis of C. albicans. In conclusion, we found evidence for RHOA-ROCK-MLC mediated mechanical force generation downstream of Dectin-1 for C. albicans phagocytosis.
Obstructive sleep apnea (OSA) is a disease characterized by intermittent hypoxemia and sleep fragmentation. Studies conducted previously to assess cognitive functions in OSA have shown variable results. OSA is one of the increasingly common disorders in India. OSA typically shows 'tip of iceberg' phenomenon, i.e. very few diagnosed cases even with high prevalence. Thus, in a country with one of the highest number of road traffic accidents and occupational accidents, it becomes even more important to assess all OSA patients for cognitive functions especially with choice reaction time which is a very good indicator of real life situations such as vehicular driving and demanding occupational task. Thus, we compared cognitive functions in 30 cases of OSA with 30 age, sex and education matched control using standardized paper based tests and choice reaction time. We found choice reaction time to be severely affected in OSA. Amongst various domains of cognition, attention and executive functions were significantly affected in OSA. Also, there was decline in psychomotor abilities and memory.
with different adhesion. These results show that mechanosensitive cell proliferation and death play a significant and not yet completely quantified role in driving tissue dynamics and structure.
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