Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Nat Commun. 2024 Oct 7;15(1):8663. doi: 10.1038/s41467-024-53060-4.
Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and COVID-19 patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.
李斯特菌(LM)具有突破多种屏障并引发复杂免疫反应的能力。然而,对于 LM 如何在体内逃避先天免疫监视,我们仍缺乏明确的认识。在这里,我们利用肝内活体成像来阐明 LM 在肝脏感染过程中的动态过程。我们发现,李斯特菌通过溶菌素 O(LLO)可以迅速从枯否细胞(KCs)中逃逸,并在肝细胞内增殖。当 LM 暴露于肝窦时,中性粒细胞迅速聚集在感染部位。随后,LM 可以诱导 I 型干扰素(IFN-I)的产生,主要在脾脏中,通过失活 ERK 途径来抑制中性粒细胞的聚集,从而逃避中性粒细胞介导的清除,从而发挥全身性作用。此外,我们的研究结果表明,病毒诱导的 IFN-I 抑制中性粒细胞聚集,COVID-19 患者表现出中性粒细胞聚集功能受损。总之,我们的研究结果提供了令人信服的证据,表明以李斯特菌为代表的胞内细菌可以劫持宿主抗病毒感染的防御机制,从而逃避免疫监视。此外,IFN-I 引起的中性粒细胞聚集功能受损是病毒感染后细菌感染易感性增加的重要因素之一。