The AIM2 inflammasome is activated in astrocytes during the late phase of EAE

Barclay, William E.; Aggarwal, Nupur; Deerhake, M. Elizabeth; Inoue, Makoto; Nonaka, Toshiaki; Nozaki, Kengo; Luzum, Nathan A.; Miao, Edward A.; Shinohara, Mari L.

doi:10.1172/jci.insight.155563

Cited by 23 publications

(25 citation statements)

References 56 publications

(101 reference statements)

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“…While innate immune sensing in astrocytes is not well understood, inflammasome activation in astrocytes has been associated with some neurodegenerative diseases. The AIM2 inflammasome was found to be activated during experimental autoimmune encephalomyelitis in astrocytes, although these cells failed to undergo cell death and had poor IL-1β expression [ 126 ]. Additionally, astroglial NLRP3 inflammasome complexes have also been reported to be involved in neuroinflammation in ALS, with higher levels of NLRP3, ASC, IL-18, and caspase-1 in comparison to non-diseased controls [ 127 ].…”

Section: Neuroinflammation Innate Immunity and Ad: A Complex Relation...mentioning

confidence: 99%

Innate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease

Rajesh

Kanneganti

2022

Cells

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Alzheimer’s disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid β (Aβ) plaques and type 2 microtubule-associated protein (Tau) abnormalities. Multiple studies have shown that many of the brain’s immunological cells, specifically microglia and astrocytes, are involved in AD pathogenesis. Cells of the innate immune system play an essential role in eliminating pathogens but also regulate brain homeostasis and AD. When activated, innate immune cells can cause programmed cell death through multiple pathways, including pyroptosis, apoptosis, necroptosis, and PANoptosis. The cell death often results in the release of proinflammatory cytokines that propagate the innate immune response and can eliminate Aβ plaques and aggregated Tau proteins. However, chronic neuroinflammation, which can result from cell death, has been linked to neurodegenerative diseases and can worsen AD. Therefore, the innate immune response must be tightly balanced to appropriately clear these AD-related structural abnormalities without inducing chronic neuroinflammation. In this review, we discuss neuroinflammation, innate immune responses, inflammatory cell death pathways, and cytokine secretion as they relate to AD. Therapeutic strategies targeting these innate immune cell death mechanisms will be critical to consider for future preventive or palliative treatments for AD.

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Section: Neuroinflammation Innate Immunity and Ad: A Complex Relation...mentioning

confidence: 99%

Innate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease

Rajesh

Kanneganti

2022

Cells

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“…Also, the NLRP3 inflammasome is not activated in astrocytes, contrasting to the NLRP3 inflammasome activation and its pathogenic role in EAE in peripheral myeloid cells 145,191‐193 . Interestingly, mouse primary astrocytes with active AIM2 inflammasome release little IL‐1β due to globally limited expression of inflammasome components 145 . The function of the AIM2 inflammasome in astrocytes is not inflammatory based on limited IL‐1β production by astrocytes and more severe EAE in Aim2 −/− mice 145,152,194 .…”

Section: Pathogen Detection By Cns‐resident Cellsmentioning

confidence: 99%

“…NLRP3 and NLRC4 inflammasomes are activated in LPC‐stimulated mouse primary astrocytes ex vivo , and resulting IL‐1β secretion was reported, 146 suggesting that astrocytes could behave as inflammatory cells through these inflammasomes. Similarly, ex vivo treatment of mouse primary astrocytes with nigericin, an NLRP3 inflammasome stimulator, also allows IL‐1β secretion, although poly(dA:dT)/liposome, an AIM2 inflammasomes stimulator, fails to secrete detectable levels of IL‐1β 145 . Human primary astrocytes express NLRP2, which can be activated by adenosine triphosphate (ATP) as a DAMP, and process pro‐caspase‐1 and pro‐IL‐1β 190 .…”

Section: Pathogen Detection By Cns‐resident Cellsmentioning

confidence: 99%

“…Our laboratory recently reported that astrocytes have activated AIM2 inflammasome in the spinal cord during a late stage of EAE 145 . Unexpectedly, astrocytes are the main CNS cell type exhibiting AIM2 inflammasome “activation”, and neither microglia nor CNS‐infiltrated myeloid cells are sources of any active inflammasomes during EAE 145 .…”

Section: Pathogen Detection By Cns‐resident Cellsmentioning

confidence: 99%

“…Unexpectedly, astrocytes are the main CNS cell type exhibiting AIM2 inflammasome “activation”, and neither microglia nor CNS‐infiltrated myeloid cells are sources of any active inflammasomes during EAE 145 . Also, the NLRP3 inflammasome is not activated in astrocytes, contrasting to the NLRP3 inflammasome activation and its pathogenic role in EAE in peripheral myeloid cells 145,191‐193 . Interestingly, mouse primary astrocytes with active AIM2 inflammasome release little IL‐1β due to globally limited expression of inflammasome components 145 .…”

Section: Pathogen Detection By Cns‐resident Cellsmentioning

confidence: 99%

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Host immune responses in the central nervous system during fungal infections

Reyes

Shinohara

2022

Immunological Reviews

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Fungal infections in the central nervous system (CNS) cause high morbidity and mortality. The frequency of CNS mycosis has increased over the last two decades as more individuals go through immunocompromised conditions for various reasons.Nevertheless, options for clinical interventions for CNS mycoses are still limited. Thus, there is an urgent need to understand the host-pathogen interaction mechanisms in CNS mycoses for developing novel treatments. Although the CNS has been regarded as an immune-privileged site, recent studies demonstrate the critical involvement of immune responses elicited by CNS-resident and CNS-infiltrated cells during fungal infections. In this review, we discuss mechanisms of fungal invasion in the CNS, fungal pathogen detection by CNS-resident cells (microglia, astrocytes, oligodendrocytes, neurons), roles of CNS-infiltrated leukocytes, and host immune responses. We consider that understanding host immune responses in the CNS is crucial for endeavors to develop treatments for CNS mycosis.

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