RESUMO
The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.
Assuntos
Humanos , DNA Bacteriano , Alergia e Imunologia , Metabolismo , DNA Viral , Alergia e Imunologia , Metabolismo , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Imunidade Inata , Fator Regulador 3 de Interferon , Genética , Alergia e Imunologia , Interferon Tipo I , Alergia e Imunologia , Proteínas de Membrana , Genética , Alergia e Imunologia , Modelos Moleculares , NF-kappa B , Genética , Alergia e Imunologia , Nucleotídeos Cíclicos , Alergia e Imunologia , Nucleotidiltransferases , Genética , Alergia e Imunologia , Ligação Proteica , Proteínas Serina-Treonina Quinases , Genética , Alergia e Imunologia , Transdução de SinaisRESUMO
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.