NOD1/NOD2 and RIP2 Regulate Endoplasmic Reticulum Stress-Induced Inflammation during Infection.

The inflammatory response to infection is likely to be multifactorial and involve a variety of ligand-dependent and -independent recognition pathways. We previously reported the presence of NOD1/NOD2-dependent endoplasmic reticulum (ER) stress-induced inflammation during infection , but the relevance of this finding to an context is unclear. Here, we examined the ER stress response to infection. The induction of interleukin 6 (IL-6) production after systemic infection correlated with expression of ER stress response genes. Furthermore, when tauroursodeoxycholate (TUDCA) was used to inhibit the ER stress response, an increased bacterial burden was detected, suggesting that ER stress-driven inflammation can contribute to systemic bacterial clearance. Mice lacking both NOD1 and NOD2 or RIP2 exhibited slightly higher systemic bacterial burdens after infection with Overall, these data suggest a model where RIP2 and NOD1/NOD2 proteins link ER stress responses with the induction of -specific inflammatory responses. Understanding the initiation of the inflammatory response during infection is of public health importance given the impact of this disease on young women in the United States. Many young women are chronically infected with but are asymptomatic and therefore do not seek treatment, leaving them at risk of long-term reproductive harm due to inflammation in response to infection. Our manuscript explores the role of the endoplasmic reticulum stress response pathway initiated by an innate receptor in the development of this inflammation.