The effect of acidic extracellular ph on direct anticryptococcal activities of nk cells
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2012
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Abstract
Cryptococcus produces a solid tumor-like mass that is called a cryptococcoma. Analogous to tumors, the cryptococcoma microenvironment can be very acidic, which presents challenges to host defense. Analogous to tumor cells, Cryptococcus can be killed by NK cells. As acidic pH inhibits NK cell anti-tumor activities, we examined if there was a similar reduction in NK cell anticryptococcal activities. Surprisingly, we found that NK cells have preserved or even enhanced killing of Cryptococcus in acidic compared to physiological pH. Acidic pH did not increase processes that might increase killing including the effector to target ratio, binding of NK cells to Cryptococcus, or the active perforin content in NK cells. By contrast, acidic pH enhanced ERKl/2 phosphorylation and perforin degranulation, which are essential for cryptococcal killing. Moreover, increased killing occurred during more rapid replication of the organisms. These results suggest that NK cells have amplified signaling, degranulation, and greater capacity to kill microbes at low pH and when the organisms replicate quickly.
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Bibliography: p. 92-111
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Citation
Islam, A. (2012). The effect of acidic extracellular ph on direct anticryptococcal activities of nk cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4759