Salmonella-NLRP3 Inflammasome Crosstalk: Host Defense Activation Versus Bacterial Immune Evasion Strategies

Yuxuan Li,1,* Ying Xu,2 Cheng Jin,1 Jiayi Qiu,1 Xinan Jiao,3– 6 Zhiming Pan,3– 6 Yaxin Guo1,3– 6,* 1School of Nursing School of Public Health, Yangzhou University, Jiangsu, People’s Republic of China; 2The Department of Economics and Management, Jiangsu College of Tourism, Jiangsu, People’s Republic of China; 3Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 4Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 5Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 6Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaxin Guo, School of Nursing School of Public Health, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China, Tel +86-15252570275, Email [email protected] Zhiming Pan, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China, Email [email protected]: The innate immune system plays a crucial role in defending against Salmonella infection. Inflammasomes are macromolecular complexes that assemble in response to the recognition of pathogen- or danger-associated molecular patterns. These complexes serve as signaling platforms for the activation of inflammatory Caspases, which subsequently triggers the maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. This process also initiates pyroptosis, a highly inflammatory form of programmed cell death characterized by lytic cell lysis. Salmonella are intracellular pathogens that proliferate within epithelial cells and macrophages, posing a significant public health risk in both developed and developing countries. During Salmonella infection, the canonical NLRP3 and NLRC4 inflammasome, as well as non-canonical inflammasome, are activated. Unlike NLRC4 and non-canonical inflammasomes, which play crucial roles during intestinal infection phases, the role of NLRP3 inflammasome in resisting Salmonella infection demonstrates a higher degree of complexity and uncertainty. Nonetheless, the activation of NLRP3 inflammasome, along with the downstream innate and adaptive responses, form a robust host immune barrier against potential pathogens. Therefore, successful pathogens must evolve multiple mechanisms to circumvent or counteract these immune barriers. Here we review and discuss the mechanisms of NLRP3 inflammasome activation triggered by intracellular Salmonella, as well as the multiple strategies employed by Salmonella to avoid or delay NLRP3 inflammasome activation. A deeper understanding of how NLRP3 inflammasomes recognize Salmonella and how pathogens evade NLRP3 activation has the potential to facilitate the development of novel prevention and control measures for Salmonella infection.Keywords: inflammasome, Salmonella, NLRP3, caspases, immune evasion