Aim2 and Nlrp3 Are Dispensable for Vaccine-Induced Immunity against Francisella tularensis Live Vaccine Strain

Alqahtani, Maha; Ma, Zhuo; Fantone, Kayla; Malik, Meenakshi; Bakshi, Chandra Shekhar

doi:10.1128/iai.00134-21

Cited by 2 publications

(2 citation statements)

References 59 publications

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“…AIM2 is a typical inflammasome assembled by the intracellular receptor ALR [ 103 ]. When intracellular pathogen DNA is detected by the HIN200 domain of AIM2, such as the DNA of Francisella tularensis and vaccinia virus [ 75 , 104 ], AIM2 will recruit ASCs to activate caspase-1. The AIM2 receptor is a member of the PYHIN (containing pyrin and HIN domains) family [ 105 , 106 ] and is characterized by its tight binding to oligonucleotides or the oligosaccharide folds between an N-terminal PYD and a C-terminal HIN domain.…”

Section: Inflammasomesmentioning

confidence: 99%

Focus on the Mechanisms and Functions of Pyroptosis, Inflammasomes, and Inflammatory Caspases in Infectious Diseases

Song

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Eukaryotic cells can initiate several distinct self-destruction mechanisms to display essential roles for the homeostasis maintenance, development, and survival of an organism. Pyroptosis, a key response mode in innate immunity, also referred to as caspase-1-dependent proinflammatory programmed necrotic cell death activated by human caspase-1/4/5, or mouse caspase-1/11, plays indispensable roles in response to cytoplasmic insults and immune defense against infectious diseases. These inflammatory caspases are employed by the host to eliminate pathogen infections such as bacteria, viruses, protozoans, and fungi. Gasdermin D requires to be cleaved and activated by these inflammatory caspases to trigger the pyroptosis process. Physiological rupture of cells results in the release of proinflammatory cytokines, the alarmins IL-1β and IL-18, symbolizing the inflammatory potential of pyroptosis. Moreover, long noncoding RNAs play direct or indirect roles in the upstream of the pyroptosis trigger pathway. Here, we review in detail recently acquired insights into the central roles of inflammatory caspases, inflammasomes, and pyroptosis, as well as the crosstalk between pyroptosis and long noncoding RNAs in mediating infection immunity and pathogen clearance.

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Section: Inflammasomesmentioning

confidence: 99%

Focus on the Mechanisms and Functions of Pyroptosis, Inflammasomes, and Inflammatory Caspases in Infectious Diseases

Song

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Nlrp3 also contributes to the IgA response vital for protection against F. tularensis LVS challenge in immunized mice (Duffy et al, 2016). However, the activation of Aim2 and Nlrp3inflammasomes are repressed in macrophages infected with F. tularensis LVS, and both are dispensable for vaccine-induced immunity against pulmonary tularemia (Atianand et al, 2011;Dotson et al, 2013;Wallet et al, 2016;Alqahtani et al, 2021). It has been reported that Nlrp3 exacerbates the symptoms of pulmonary tularemia primarily by causing excessive infiltration of immature neutrophils in the lungs of mice infected with F. tularensis, indicating a pathogenic role for Nlrp3 (Periasamy et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Nlrp3 Increases the Host’s Susceptibility to Tularemia

et al. 2021

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Francisella tularensis (F. tularensis) is a Gram-negative, intracellular bacterium and the causative agent of a fatal human disease known as tularemia. The CDC has classified F. tularensis as a Tier 1 Category A select agent based on its ease of aerosolization, low infectious dose, past use as a bioweapon, and the potential to be used as a bioterror agent. Francisella has a unique replication cycle. Upon its uptake, Francisella remains in the phagosomes for a short period and then escapes into the cytosol, where the replication occurs. Francisella is recognized by cytosolic pattern recognition receptors, Absent In Melanoma 2 (Aim2) and Nacht LRR and PYD domains containing Protein 3 (Nlrp3). The recognition of Francisella ligands by Aim2 and Nlrp3 triggers the assembly and activation of the inflammasome. The mechanism of activation of Aim2 is well established; however, how Nlrp3 inflammasome is activated in response to F. tularensis infection is not known. Unlike Aim2, the protective role of Nlrp3 against Francisella infection is not fully established. This study investigated the role of Nlrp3 and the potential mechanisms through which Nlrp3 exerts its detrimental effects on the host in response to F. tularensis infection. The results from in vitro studies demonstrate that Nlrp3 dampens NF-κB and MAPK signaling, and pro-inflammatory cytokine production, which allows replication of F. tularensis in infected macrophages. In vivo, Nlrp3 deficiency results in differential expression of several genes required to induce a protective immune response against respiratory tularemia. Nlrp3-deficient mice mount a stronger innate immune response, clear bacteria efficiently with minimal organ damage, and are more resistant to Francisella infection than their wild-type counterparts. Together, these results demonstrate that Nlrp3 enhances the host’s susceptibility to F. tularensis by modulating the protective innate immune responses. Collectively, this study advances our understanding of the detrimental role of Nlrp3 in tularemia pathogenesis.

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Aim2 and Nlrp3 Are Dispensable for Vaccine-Induced Immunity against Francisella tularensis Live Vaccine Strain

Cited by 2 publications

References 59 publications

Focus on the Mechanisms and Functions of Pyroptosis, Inflammasomes, and Inflammatory Caspases in Infectious Diseases

Focus on the Mechanisms and Functions of Pyroptosis, Inflammasomes, and Inflammatory Caspases in Infectious Diseases

Nlrp3 Increases the Host’s Susceptibility to Tularemia

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