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Abstract
The innate immune system confers first-line defense against various pathogens including bacteria and viruses. Early detection of invading pathogens by the host depends on a limited number of specific pattern recognition receptors (PRRs) that detect pathogen associated molecular patterns (PAMPs) and activate signal transduction cascades that lead to activation of defense mechanisms. Among those sensors, RIG-I-like receptors (RLRs) play crucial roles in the detection of viruses by recognizing intracellular viral patterns such as viral RNAs to induce type-I interferon production. The discovery of intracellular RNA sensing mechanism by RIG-I prompted the investigations to find out intracellular DNA sensors. Recently, several proteins including DAI, AIM2, IFI16, and cGAS have been suggested as DNA sensing molecules to detect DNA viruses and bacteria, suggesting there are multiple receptors for microbial DNA. In this review, we discuss the current our understanding of sensing microbial DNA and subsequent induction of immune responses.
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Figure 1.
Induction of type-I interferon by intracellular DNA sensors. It has been shown that intracellular DNA sensors including DNA-dependent activator of interferon-regulatory factors (DAI), RNA polymerase III (RNA Pol III), Leucine rich repeat interacting protein 1 (LRRFIP1), Cyclic GMP-AMP synthase (cGAS), (DExD/H)-box helicase 9/36 (DHX9/36) can induce type-I interferon production upon recognition of pathogen-derived DNA.
Figure 2.
Activation of inflammasome signaling by intracellular DNA sensors. Absent in melanoma 2 (AIM2) and gamma-interferon-inducible protein 16 (IFI16) activate inflammasome signaling pathway leading to caspase-1 activation upon recognition of pathogen-derived DNA.
Table 1.
List of cytosolic DNA sensors.
| DNA sensors | Related pathogens | Ligand | |
|---|---|---|---|
| Type-I interferon induction |
DAI1 RNA Pol III2 DHX9/DHX363 DDX414 LRRFIP15 cGAS6 |
HSV1a HSV1, Adenovirus, EBVb, L. pneumophiliac HSV1 HSV1, Adenovirus VSVd, L. monocytogenese HSV1 |
dsDNA dsDNA CpG DNA dsDNA dsDNA, dsRNA dsDNA |
| Inflammasome activation |
AIM27 IFI168 |
F. tulalensisf, L. monocytogenes, VVg, mCMVh HSV1, KSHVi |
dsDNA dsDNA |
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