Working in mice with and without the Nlrp6 gene, researchers tracked the immune response to different bacteria agents. This study focused on the innate immune response to Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. All are bacteria that spread through food with potentially deadly results.
Surprisingly, mice without NLRP6 were far more likely to survive infection with lethal doses of the bacteria than their normal counterparts. The NLRP6-deficient mice had fewer bacteria in their livers and spleens one and three days after infection. They also had higher than normal levels of monocytes and neutrophils in circulation. Those are white blood cells known to play an important early role in combating infections. The findings suggest that mice lacking NLRP6 mount a more effective immune response.
Researchers went on to show that NLRP6 suppressed activity in pathways that trigger production of proteins called cytokines, which promote inflammation to combat the infection. The results show that NLRP6 regulates the nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) pathways.
"The result was entirely unexpected," said Paras Anand, Ph.D., a postdoctoral fellow in Kanneganti's laboratory and the study's first author. "This is the first member from the NLR family of proteins that inhibits rather than activates pathways involved in the innate immune response."
"NLRP6 might represent an entirely new subclass of these NLR proteins that functions to impede bacterial clearance," he said. Investigators are now studying the protein's response to other infectious agents.
Previous work on this molecule demonstrated that NLRP6 also helps to limit colitis and colon cancer. Kanneganti said the findings underscore the importance of balance to a properly functioning immune system. "This molecule helps maintain a balance between promoting and suppressing inflamma
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St. Jude Children's Research Hospital