Innate immunity is the first arm of the immune system to be triggered in host defense against intracellular pathogens. Some pathogens during evolution have developed stealthy strategies to bypass innate surface receptors but when they reach host cell cytosol they are recognized by cytosolic receptors. Professional phagocytes, such as macrophages, neutrophils, or dendritic cells, have the specialized ability to internalize pathogens into membrane-bound compartments, termed phagosomes.

Additionally, pathogen phagocytosis effectively guarantees the concentrated delivery of pathogen-associated
molecular patterns (PAMPs) inside cells. Some pathogens can exit phagosomes and survive and replicate in the cytosolic space. Several pattern recognition receptors (PRR) have been described over the years. A diverse repertoire of PRRs exists, localized freely in the cytosol or associated with or integrated into cytoplasmic membranes, to detect these organisms. Among these intracellular sensors, several molecules have been identified such as cGAS/STING pathway, the inflammasome platforms (eg: NLRP3, NLRC4, AIM2), caspase-11/4/5, RIG-I, among others. Host cell activation through these receptors leads to cell signaling pathways resulting in inflammatory and anti-inflammatory reactions.

In this research topic, we would like to contribute to the understanding of cytosolic detection of infections by immune cells. We intend to unravel the rules governing when and how PAMPs get access to be sensed by cytosolic receptors and how pathogens modify their PAMPs to escape cytosolic recognition. Manuscripts dealing with bacterial, viral, fungal, or protozoan intracellular infections are welcome in any type of article that Frontiers in Immunology publishes covering the following topics:

• Cytosolic sensing of intracellular pathogens
• How intracellular pathogens escape innate immune recognition
• Stress responses induced by intracellular infections and the impact on the immune system
• Trained immunity and innate memory
• The role of caspases in intracellular sensing
• The role of guanylate-binding proteins (GBP) and other GTPases in PAMPs sensing

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