Innate immunity is the first arm of the immune system to be triggered in host defense against intracellular pathogens and cancer. 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. Also, cancer cells have learned how to escape innate immune surveillance.

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. Some of these receptors such as cGAS-STING pathway has also a prominent role in crosstalk between innate and adaptive immunity against different type of cancer.

In this research topic, we would like to contribute to the understanding of innate immune sensing of pathogens and cancer 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. Also the escape of cancer cells of the immunosurveillance is focused of this research topic. Manuscripts dealing with bacterial, viral, fungal, or protozoan intracellular infections and different type of cancer are welcome in any type of article that Frontiers in Immunology publishes covering the following topics:

• Cytosolic sensing of intracellular pathogens an cancer

• How intracellular pathogens and cancer cells 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”

• How innate and adaptive immunity interfere in cancer immunotherapy

Are you interested in contributing a manuscript to this Research Topic?

The Role of Cytosolic Sensors in Host Defense to Intracellular Pathogens and Cancer