Negative Regulators of Innate Immunity and their Role in Host Responses to Injury and Infection

Every organism must recognize damage-associated and pathogen-associated molecular patterns (DAMPs and PAMPs) to react rapidly. The immune system requires potent negative regulators to control unnecessary or overshooting responses and balance the homeostasis in all tissues. A significant number of negative regulators of pattern recognition receptors (PRR) consist of modified innate sensors and downstream molecules that regulate inflammatory signals initiated by sterile, damage-associated inflammation as well as responses to pathogens. These conserved mechanisms contribute to immune homeostasis, maintain a constant number of immune cells, and limit the activation of the cells during frequent stimulations by antigens. The same mechanisms enable maintaining the symbiotic relationship between host and tissue microbiota. Moreover, negative regulators of PRRs play a fundamental role in the training of the host immune system and the development of immune tolerance. They ensure that the response of immune cells is precise and potent enough to eliminate the source of inflammation but do not develop into fatal inflammatory disease. The complex cellular environment in which cells are organized allows interactions between different cell types. Various environmental signals determine their phenotype, the degree of maturation, and responses. Regulatory mechanisms and molecules determine the necessity and efficiency of host defense, disease progression, and restoring of the homeostasis. Various studies have revealed the crucial role of homeostasis and mechanisms of immune-control under physiological and pathological conditions, as well as their substantial potential as a target in clinical applications. However, the molecular instruments that reshape the tissue responses remain poorly understood.

In this Research Topic, we welcome contributions as Original Research, Reports, Case Reports, Reviews, Mini Reviews, and Perspective articles focusing on immunomodulatory molecules in the context of the host response to pathogen and tissue injury. Manuscripts on the following subtopics are welcome:

1. Regulation of inflammatory responses by negative regulators of diverse PRRs (TLRs, NLRs, RLRs, CLRs, etc.)
2. Maintaining of tissue homeostasis and disorders caused by an imbalance between triggers and negative regulators
3. Strategies used by pathogens targeting modifications of negative regulators