上海士锋生物：蛋白NLRP6抵御细菌感染

研究者表示，这项研究的亮点在于如果可以产生出单克隆中和抗体来中和这种蛋白质，就能有效抵御细菌的感染。尽管目前部分抗生素对于抵御细菌感染有效，可是细菌的变异会慢慢产生耐药性，这给人类的健康和财产带来了巨大损失。更好地理解免疫系统如何识别以及对于病原体产生效应，对于我们开发出新的有效疗法会带来巨大帮助。

研究者前期重点研究了类似NOD的受体蛋白6（NLRP6），NLRP6属于先天免疫应答的部分组分蛋白家族，这些蛋白质在细胞内部充当了哨兵的角色，可以识别并且对于病原体感染产生效应，截至到现在没有人知道NLRP6所扮演的角色。通过研究有无Nlrp6基因的小鼠，研究者研究了小鼠对于不同细菌的免疫效应，这些细菌包括单核李斯特氏菌、鼠伤寒沙门菌以及大肠杆菌。结果显示，无Nlrp6基因的小鼠在注射致死剂量的细菌菌液之后更容易生存，而且这种小鼠的肝脏和脾脏在感染细菌一天和三天之后含有少量的细菌，而且其体内含有高水平的单核细胞和中性白细胞，综上所述，缺失NLRP6的小鼠表现出了更强效应的免疫效应。

研究者进而揭示了NLRP6受压制的活性可以触发细胞因子等蛋白质的产生，这将促进炎症来抵御感染，结果揭示出NLRP6可以调节核因子κB和胞外信号调节激酶途径。研究者Paras表示，研究结果*出乎意料，这是NLR家族的*个成员被报道可以抑制而并非激活先天性免疫效应。这项研究由国立卫生研究院和ALSAC支持。

编译自：Innate Immune System Protein Provides a New Target in War Against Bacterial Infections

原文摘要：

NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens

Members of the intracellular nucleotide-binding and oligomerization domain （NOD）-like receptor （NLR） family contribute to immune responses through activation of nuclear factor-κB （NF-κB）, type I interferon and inflammasome signalling. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis, but the role of NLRP6 in microbial infections and the nature of the inflammatory signalling pathways regulated by NLRP6 remain unclear. Here we show thatNlrp6-deficient mice are highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signalling in both haematopoietic and radioresistant cells contributed to increased susceptibility. Nlrp6 deficiency enhanced activation of mitogen-activated protein kinase （MAPK） and the canonical NF-κB pathway after Toll-like receptor ligation, but not cytosolic /2 ligation, in vitro. Consequently, infected Nlrp6-deficient cells produced increased levels of NF-κB- and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signalling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and -negative bacterial pathogens.