The crosstalk between pattern-recognition receptor signaling and calcium signaling

Abstract

The innate immune system is the first line of host defense, and it is capable of resisting both exogenous pathogenic challenges and endogenous danger signals via different pattern recognition receptors (PRRs), including Toll-like receptors, retinoic acid-inducible gene-1 (RIG-1)-like receptors, cytosolic DNA sensors, as well as nucleotide-binding oligomerization domain (NOD)-like receptors. After recognizing the pathogen-associated molecular patterns from exogenous microbes or the damage-associated molecular patterns from endogenous immune-stimulatory signals, these PRRs signaling pathways can induce the expression of interferons and inflammatory factors against microbial pathogen invasion and endogenous stresses. Calcium (Ca2+) is a second messenger that participates in the modulation of various biological processes, including survival, proliferation, apoptosis, and immune response, and is involved in diverse diseases, such as autoimmune diseases and virus infection. To date, accumulating evidence elucidated that the PRR signaling exhibited a regulatory effect on Ca2+ signaling. Meanwhile, Ca2+ signaling also played a critical role in controlling biological processes mediated by the PRR adaptors. Since the importance of these two signalings, it would be interesting to clarify the deeper biological implications of their interplays. This review focuses on the crosstalk between Ca2+ signaling and PRR signaling to regulate innate immune responses.