Structures and Mechanisms in the cGAS-STING Innate Immunity Pathway

Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women ( n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in the same KEEPS participants 4 yr after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β-estradiol (50 μg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Twenty SNPs within the innate immunity pathway most related with CIMT after 4 yr were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, single nucleotide polymorphisms (SNPs) within the innate immunity pathway were found to alter the treatment effect on 4 yr change in CIMT (i.e., significant interaction between treatment and genetic variation in the innate immunity pathway; P < 0.001). No SNPs by treatment effects were observed with changes of CAC >5 Agatston units after 4 yr. Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT.

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A case–control study of innate immunity pathway gene polymorphisms in Puerto Ricans reveals association of toll-like receptor 2 +596 variant with asthma

BMC Pulmonary Medicine ◽

10.1186/s12890-016-0272-7 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Mario G. Ortiz-Martínez ◽

Orquídea Frías-Belén ◽

Sylvette Nazario-Jiménez ◽

María López-Quintero ◽

Rosa I. Rodríguez-Cotto ◽

...

Keyword(s):

Innate Immunity ◽

Gene Polymorphisms ◽

Case Control Study ◽

Puerto Ricans ◽

Case Control ◽

Toll Like Receptor ◽

Pathway Gene ◽

Toll Like Receptor 2 ◽

Innate Immunity Pathway ◽

Control Study

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Beta-catenin inhibits bovine parainfluenza virus type 3 replication via innate immunity pathway

BMC Veterinary Research ◽

10.1186/s12917-020-02291-w ◽

2020 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Xinying Du ◽

Wenqi He ◽

Hongbin He ◽

Hongmei Wang

Keyword(s):

Innate Immunity ◽

Virus Type ◽

Parainfluenza Virus ◽

Beta Catenin ◽

Innate Immunity Pathway ◽

Type 3 ◽

Bovine Parainfluenza Virus

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The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels

Experimental & Molecular Medicine ◽

10.1038/s12276-020-0416-y ◽

2020 ◽

Vol 52 (4) ◽

pp. 643-657 ◽

Cited By ~ 6

Author(s):

Abdul Basit ◽

Min-Guk Cho ◽

Eui-Yun Kim ◽

Dohyeong Kwon ◽

Suk-Jo Kang ◽

...

Keyword(s):

Innate Immunity ◽

Adverse Effects ◽

Cancer Cells ◽

Chromosomal Instability ◽

Interferon Regulatory Factor ◽

Mitotic Arrest ◽

Regulatory Factor ◽

Chromosome Missegregation ◽

Sting Pathway ◽

Innate Immunity Pathway

Abstract Chromosomal instability (CIN) in cancer cells has been reported to activate the cGAS–STING innate immunity pathway via micronuclei formation, thus affecting tumor immunity and tumor progression. However, adverse effects of the cGAS/STING pathway as they relate to CIN have not yet been investigated. We addressed this issue using knockdown and add-back approaches to analyze each component of the cGAS/STING/TBK1/IRF3 pathway, and we monitored the extent of CIN by measuring micronuclei formation after release from nocodazole-induced mitotic arrest. Interestingly, knockdown of cGAS (cyclic GMP-AMP synthase) along with induction of mitotic arrest in HeLa and U2OS cancer cells clearly resulted in increased micronuclei formation and chromosome missegregation. Knockdown of STING (stimulator of interferon genes), TBK1 (TANK-binding kinase-1), or IRF3 (interferon regulatory factor-3) also resulted in increased micronuclei formation. Moreover, transfection with cGAMP, the product of cGAS enzymatic activity, as well as add-back of cGAS WT (but not catalytic-dead mutant cGAS), or WT or constitutively active STING (but not an inactive STING mutant) rescued the micronuclei phenotype, demonstrating that all components of the cGAS/STING/TBK1/IRF3 pathway play a role in preventing CIN. Moreover, p21 levels were decreased in cGAS-, STING-, TBK1-, and IRF3-knockdown cells, which was accompanied by the precocious G2/M transition of cells and the enhanced micronuclei phenotype. Overexpression of p21 or inhibition of CDK1 in cGAS-depleted cells reduced micronuclei formation and abrogated the precocious G2/M transition, indicating that the decrease in p21 and the subsequent precocious G2/M transition is the main mechanism underlying the induction of CIN through disruption of cGAS/STING signaling.

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Infection of human islets of langerhans with two strains of coxsackie B virus serotype 1: Assessment of virus replication, degree of cell death and induction of genes involved in the innate immunity pathway

Journal of Medical Virology ◽

10.1002/jmv.23835 ◽

2013 ◽

Vol 86 (8) ◽

pp. 1402-1411 ◽

Cited By ~ 25

Author(s):

Mahesh Anagandula ◽

Sarah J. Richardson ◽

M. Steven Oberste ◽

Amir-Babak Sioofy-Khojine ◽

Heikki Hyöty ◽

...

Keyword(s):

Innate Immunity ◽

Cell Death ◽

Virus Replication ◽

Human Islets ◽

Virus Serotype ◽

B Virus ◽

Coxsackie B Virus ◽

Serotype 1 ◽

Innate Immunity Pathway ◽

Coxsackie B

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Identification of two QTLs, BPH41 and BPH42, and their respective gene candidates for brown planthopper resistance in rice by a combinatorial approach of QTL mapping and RNA-seq

10.21203/rs.3.rs-979035/v1 ◽

2021 ◽

Author(s):

Han Qi Tan ◽

Sreekanth Palyam ◽

Jagadeesha Gouda ◽

Prakash Kumar ◽

Santhosh Kumar Chellian

Keyword(s):

Innate Immunity ◽

Brown Planthopper ◽

Resistance Mechanism ◽

Rna Seq ◽

Rice Varieties ◽

Major Pest ◽

Differential Gene ◽

Brown Planthopper Resistance ◽

Innate Immunity Pathway ◽

Successful Production

Abstract The brown planthopper (BPH) is the leading cause of insect damage to rice plants. It has caused profound losses in rice production since the late 1970’s and continues to be a major pest problem. Therefore, there is an urgent need to discover new BPH resistance genes to ensure the successful production of rice. Here, a new BPH resistance source provided by SeedWorks International Pvt. Ltd., SWD10, was used for this purpose. A total of 232 F2 progenies were genotyped with 216 polymorphic markers. Results revealed two dominant QTLs located on the short and long arms of chromosome 4. These QTLs are referred to as BPH41 and BPH42, respectively. BPH resistance mechanism test revealed that antibiosis and antixenosis mechanisms both play a role in BPH resistance conferred by these two QTLs. To further reduce the size of each QTL, 14,368 recombinant lines were screened, and the QTLs were delimited between markers SWRm_01617 and SWRm_01522 for BPH41, and SWRm_01695 and SWRm_00328 for BPH42. Additionally, using RNA-seq data of lines containing the QTLs, we further shortlisted four and three gene candidates for BPH41 and BPH42, respectively. Differential gene expression analysis of lines containing the QTLs suggested that SWD10 BPH resistance is contributed by the plant’s innate immunity and the candidate genes may be part of the rice innate immunity pathway. The newly identified QTLs are currently being utilized for breeding BPH resistant rice varieties and hybrids.

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