AIM2 co-immunization favors specific multifunctional CD8+ T cell induction and ameliorates coxsackievirus B3-induced chronic myocarditis

Chai, Dafei; Yan, Ye; Xu, Wei; Dong, Chunsheng; Xiong, Sidong

doi:10.1016/j.antiviral.2015.04.015

Cited by 14 publications

(17 citation statements)

References 51 publications

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“…Three recent studies showed that immunization of mice against coxsackie virus B3 (CVB3) using AIM2 as a mucosal adjuvant had beneficial effects. Indeed compared to mice immunized with CVB3‐specific chitosan‐pVP1, co‐immunization of mice with CVB3‐chitosan‐pVP1 and chitosan‐pAIM2 conferred better resistance to CVB3‐induced myocarditits, increased secretory IgA, increased CVB3‐specific T cells responses and increased counts of CD8 + memory T cells …”

Section: Aim2 Detection Of Dnamentioning

confidence: 98%

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lugrin

Martinon

2017

Immunological Reviews

290

205

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Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. This triggers the maturation and secretion of the cytokines IL-1β and IL-18. It can also initiate pyroptosis, a proinflammatory form of cell death. The AIM2 inflammasome contributes to physiological responses and diseases. It is a key player in host defenses, but its deregulation can contribute immune-linked diseases, such as autoinflammatory and autoimmune pathologies. Moreover, AIM2 may play a role in cancer development. Recent studies have shown that the detection of self-DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity.

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Section: Aim2 Detection Of Dnamentioning

confidence: 98%

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lugrin

Martinon

2017

Immunological Reviews

290

205

View full text Add to dashboard Cite

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“…CS-pAIM2/CS-pVP1 vaccine alleviate the CVB3-induced acute myocarditis (Chai et al, 2014). We also have demonstrated that CS-pAIM2/CS-pVP1 vaccine alleviate the CVB3-induced chronic myocarditis by enhancing the immunogenicity of immunogenic antigens and efficiently inducing mucosal T cell immune responses with intranasal immunization (Chai et al, 2015). In the present study, the results show that AIM2 co-immunization with VP1 could mount long-lasting immune responses against acute viral myocarditis.…”

Section: Discussionmentioning

confidence: 99%

AIM2 Co-immunization with VP1 Is Associated with Increased Memory CD8 T Cells and Mounts Long Lasting Protection against Coxsackievirus B3 Challenge

Yin

Chai

Yan

et al. 2017

Front. Cell. Infect. Microbiol.

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The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals. We observed that the protection of pAIM2/pVP1 vaccine against CVB3 challenge was evidenced by significantly improved cardiac function, reduced myocardial injuries, and increased survival rate when compared with immunization with pVP1. Co-immunization with pAIM2/pVP1 robustly augmented T lymphocytes proliferation and CVB3-specific cytotoxic T lymphocyte responses. Importantly, 16 weeks after the last immunization, pAIM2/pVP1 co-immunization significantly enhanced the expression of Bcl-6, SOCS3, and Sca-1 which are critical for memory CD8 T cells as compared with pVP1 immunization. Notably, CD8 T cells that are likely vaccine-induced memory T cells were responsible for the protective efficacy of pAIM2/pVP1 vaccine by abolition of a CD8 T cell immune response following a lethal dose of CVB3 infection. Our results indicate that AIM2-adjuvanted vaccine could be a potential and promising approach to promote a long-lasting protection against CVB3-induced myocarditis.

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“…T cell reactivity against AIM2 has been found in patients with melanoma, suggesting that AIM2‐derived peptides are an ideal candidate for immunomonitoring 95 . Indeed, as a sensor of DNA, AIM2 induces an antigen‐specific antibody response and is used as an adjuvant to enhance therapeutic efficacy through CD8 + T cell adaptive immunity 39–42 . For example, AIM2 promotes the multifunctional CD8 + T cell activation elicited by the viral capsid protein 1 vaccine, 39 which favors long‐lasting protection against Coxsackievirus B 3 ‐induced myocarditis 40 .…”

Section: Role Of Aim2 In Immune Cellsmentioning

confidence: 99%

The complex role of AIM2 in autoimmune diseases and cancers

Zhu

Zhao

Chang

et al. 2021

Immunity Inflam & Disease

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Absent in melanoma 2 (AIM2) is a novel member of interferon (IFN)‐inducible PYHIN proteins. In innate immune cells, AIM2 servers as a cytoplasmic double‐stranded DNA sensor, playing a crucial role in the initiation of the innate immune response as a component of the inflammasome. AIM2 expression is increased in patients with systemic lupus erythematosus (SLE), psoriasis, and primary Sjogren's syndrome, indicating that AIM2 might be involved in the pathogenesis of autoimmune diseases. Meanwhile, AIM2 also plays an antitumorigenesis role in an inflammasome independent‐manner. In melanoma, AIM2 is initially identified as a tumor suppressor factor. However, AIM2 is also found to contribute to lung tumorigenesis via the inflammasome‐dependent release of interleukin 1β and regulation of mitochondrial dynamics. Additionally, AIM2 reciprocally dampening the cGAS‐STING pathway causes immunosuppression of macrophages and evasion of antitumor immunity during antibody treatment. To summarize the complicated effect and role of AIM2 in autoimmune diseases and cancers, herein, we provide an overview of the emerging research progress on the function and regulatory pathway of AIM2 in innate and adaptive immune cells, as well as tumor cells, and discuss its pathogenic role in autoimmune diseases, such as SLE, psoriasis, primary Sjogren's syndrome, and cancers, such as melanomas, non‐small‐cell lung cancer, colon cancer, hepatocellular carcinoma, renal carcinoma, and so on, hopefully providing potential therapeutic and diagnostic strategies for clinical use.

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AIM2 co-immunization favors specific multifunctional CD8+ T cell induction and ameliorates coxsackievirus B3-induced chronic myocarditis

Cited by 14 publications

References 51 publications

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

AIM2 Co-immunization with VP1 Is Associated with Increased Memory CD8 T Cells and Mounts Long Lasting Protection against Coxsackievirus B3 Challenge

The complex role of AIM2 in autoimmune diseases and cancers

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