Misregulation of the broad-range phospholipase C activity increases the susceptibility of Listeria monocytogenes to intracellular killing by neutrophils

作者：Blank Bryant S; Abdallah Delbert S Abi; Park Justin J; Nazarova Evgeniya V; Bitar Alan Pavinski; Maurer Kirk J; Marquis Helene^*

来源：Microbes and Infection, 2014, 16(2): 104-113.

DOI：10.1016/j.micinf.2013.10.014

• Listeria monocytogenes
• Phospholipase C
• Host pathogen interactions
• Innate immunity
• Mitochondria
• Neutrophils

Listeria monocytogenes is a facultative intracellular bacterial pathogen that tightly regulates the activities of various virulence factors during infection. A mutant strain (the plcB Delta pro mutant) that has lost the ability to control the activity of a phospholipase C (PC-PLC) is attenuated a hundred fold in mice. This attenuation is not due to a lack of bacterial fitness, but appears to result from a modified host response to infection. The transcriptomic pattern of immune-related genes indicated that PC-PLC did not enhance the innate immune response in infected macrophages. However, it partially protected the cells from bacteria-mediated mitochondrial fragmentation. In mice, the plcB Delta pro mutant transiently caused an increase in liver pathology, as judged by the size of neutrophil-filled micro-abscesses. Moreover, the plcB Delta pro mutant was more susceptible to intracellular killing by neutrophils than wild-type L. monocytogenes. Together, these data indicate that in vivo attenuation of the plcB Delta pro mutant results from its reduced ability to disrupt mitochondrial homeostasis and to resist intracellular killing by neutrophils.

• 出版日期2014-2