Abstract
The first line of host defense against infectious agents involves activation of innate immune signaling pathways that recognize specific pathogen-associated molecular patterns (PAMPs). Key triggers of innate immune signaling are now known to include microbial-specific nucleic acid, which is rapidly detected in the cytosol of the cell. For example, RIG-I-like receptors (RLRs) have evolved to detect viral RNA species and to activate the production of host defense molecules and cytokines that stimulate adaptive immune responses. In addition, host defense countermeasures, including the production of type I interferons (IFNs), can also be triggered by microbial DNA from bacteria, viruses and perhaps parasites and are regulated by the cytosolic sensor, stimulator of interferon genes (STING). STING-dependent signaling is initiated by cyclic dinucleotides (CDNs) generated by intracellular bacteria following infection. CDNs can also be synthesized by a cellular synthase, cGAS, following interaction with invasive cytosolic self-DNA or microbial DNA species. The importance of STING signaling in host defense is evident since numerous pathogens have developed strategies to prevent STING function. Here, we review the relevance of STING-controlled innate immune signaling in host defense against pathogen invasion, including microbial endeavors to subvert this critical process.
Highlights
The innate immune system comprises the foremost line of host defense to counter invasive microbial agents[1,2]
NLRs can recognize pathogen-associated molecular patterns (PAMPs) as well as damage-associated molecular patterns (DAMPs), including uric acid released by damaged cells, which trigger
This activity occurs because the cytosol is generally a DNA-free zone, and the existence of such nucleic acids usually signifies the arrival of an invading intracellular microbe or even leaked self-DNA from the nucleus as a result of DNA damage events
Summary
The innate immune system comprises the foremost line of host defense to counter invasive microbial agents[1,2]. Over the past two decades, host pattern-recognition receptors (PRRs) have been shown to play a key role in recognizing non-self, pathogen-associated molecular patterns (PAMPs). A variety of PRRs have been reported, including the Toll-like receptors (TLRs), nucleotidebinding oligomerization domain (NOD)-like receptors (NLRs) and RIG-I-like receptors (RLRs)[1]. TLRs recognize extracellular or endosomal PAMPs, such as lipopolysaccharide (LPS), flagellin, single-stranded RNA, doublestranded RNA, and CpG DNA, to activate signaling through NF-κB, interferon regulatory factor (IRF) and MAP kinase signaling pathways, which induce cytokine production[2]. NLRs can recognize PAMPs as well as damage-associated molecular patterns (DAMPs), including uric acid released by damaged cells, which trigger
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