困難梭狀桿菌是一種會產生孢子的厭氧菌，並且是造成院內感染的主因之一，特別是對服用抗生素治療的住院病人，造成抗生素相關的腹瀉，嚴重則導致偽膜性腸炎以及毒性巨結腸症。儘管先前研究已指出困難梭狀桿菌的毒素可以活化Pyrin炎性體。然而目前對於宿主先天性免疫反應如何對抗困難梭狀桿菌的菌體仍然很不清楚。在我們先前的研究發現非產毒素困難梭狀桿菌會引發非NLRP3所誘導之炎性體的活化。而在本研究中更進一步的驗證困難梭狀桿菌引發的炎性體活化主要是透過NLRP1來調控。同時並証實ASC在NLRP1炎性體活化過程中是可以不被需要的。從感染小鼠大腸組織切片的免疫螢光染色也同樣看到NLRP1及炎性體相關的蛋白表現明顯增加，並與Caspase-1聚集在相同位置。此外，我們也發現到困難梭狀桿菌的主要表面層蛋白Surface layer protein (SLP)會引發NLRP1炎性體的活化，並且具有和Nucleotide-binding oligomerization domain-containing protein 2 (NOD2)直接交互作用的能力。而NLRP1和NOD2在困難梭狀桿菌感染後是有交互作用的。在困難梭狀桿菌感染的小鼠大腸切片中，NOD2也有很高的表現量。在本篇，我們發現困難梭狀桿菌透過SLP，藉由NOD2引發了NLRP1炎性體活化。

Clostridium difficile is an obligate anaerobic pathogen that causes nosocomial infection especially in antibiotics-treated hospitalized patients. Although clostridial toxin-induced inflammasome activation has been demonstrated through Pyrin, how host innate immunity recognize C. difficile pathogen is still unknown. Previously, we found that C. difficile pathogen induced a NLRP3-independent inflammasome activation. Here, C. difficile pathogen induced inflammasome activation was further confirmed through NLRP1 by artificial reconstitution system. ASC was dispensable for C. difficile induced NLRP1 inflammasome activation. Immunofluorescence staining also demonstrated that NLRP1 and related inflammasome components were upregulated in colon tissues from C. difficile infected mice. Moreover, we found surface layer proteins (SLPs) of C. difficile, predominant outer surface components, were contributed to induce NLRP1 inflammasome activation. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) which mediates anthrax toxin induced NLRP1 inflammasome activation was highly expressed in C. difficile infected colon tissues. SLPs directly interacted with NOD2, and NOD2 interacted with NLRP1 after C. difficile infection. Taken together, this study demonstrated that C. difficile induced NLRP1 inflammasome activation through SLPs interacting with NOD2-NLRP1 pathway.

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