Natterin an aerolysin-like fish toxin drives IL-1β-dependent neutrophilic inflammation mediated by caspase-1 and caspase-11 activated by the inflammasome sensor NLRP6

Lima, Carla; Falcão, Maria Alice Pimentel; Andrade‐Barros, Aline Ingrid; Seni-Silva, Ana Carolina; Grund, Lidiane Zito; Balogh, Enikő; Conceição, Kátia; Queniaux, Valerie F.; Ryffel, Bernhard; Lopes-Ferreira, Mônica

doi:10.1016/j.intimp.2020.107287

Cited by 15 publications

(19 citation statements)

References 73 publications

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“…We confirmed Natterin from the V Tn as a pro-inflammatory molecule inducing in mice local and systemic neutrophilic inflammation dependent on the signals derived from IL-33/ST2 and IL-1β/IL-1R1, as well as IL-1α. Interestingly, the Natterin-dependent neutrophilic inflammation was mediated by the activation of both caspase-1 and caspase-11 by the non-canonical NLRP6 and NLRC4 adaptors through ASC interaction of the inflammasome complex, independent of NLRP3 [ 119 ].…”

Section: Resultsmentioning

confidence: 99%

The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function

Lima

Disner

Falcão

et al. 2021

Toxins

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Since the first record of the five founder members of the group of Natterin proteins in the venom of the medically significant fish Thalassophryne nattereri, new sequences have been identified in other species. In this work, we performed a detailed screening using available genome databases across a wide range of species to identify sequence members of the Natterin group, sequence similarities, conserved domains, and evolutionary relationships. The high-throughput tools have enabled us to dramatically expand the number of members within this group of proteins, which has a remote origin (around 400 million years ago) and is spread across Eukarya organisms, even in plants and primitive Agnathans jawless fish. Overall, the survey resulted in 331 species presenting Natterin-like proteins, mainly fish, and 859 putative genes. Besides fish, the groups with more species included in our analysis were insects and birds. The number and variety of annotations increased the knowledge of the obtained sequences in detail, such as the conserved motif AGIP in the pore-forming loop involved in the transmembrane barrel insertion, allowing us to classify them as important constituents of the innate immune defense system as effector molecules activating immune cells by interacting with conserved intracellular signaling mechanisms in the hosts.

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Section: Resultsmentioning

confidence: 99%

The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function

Lima

Disner

Falcão

et al. 2021

Toxins

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“…Former studies revealed that NLRP3 and IL-1β are highly expressed in NPs from subjects with CRSwNP, and are significantly correlated with neutrophilic nasal polyps 16 – 19 . Therefore, we investigated whether PVP-I can suppress the mucosal inflammation of neutrophilic CRS, which is related with increased expressions of NLRP3 inflammasome and associated molecules and inflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

“…The NLRP3 and its downstream IL-1β were identified as potent inducers of neutrophilic inflammation in various inflammatory diseases 16 , 17 . Previous studies showed that NLRP3 was highly expressed in nasal polyps (NPs) from subjects with CRSwNP, and significantly correlated with neutrophilic nasal polyps 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

Povidone iodine suppresses LPS-induced inflammation by inhibiting TLR4/MyD88 formation in airway epithelial cells

Lee

Choi

Chung

et al. 2022

Sci Rep

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Povidone-iodine (PVP-I) is an antiseptic and a disinfectant with broad-spectrum antimicrobial activity against various pathogens. However, it is unclear whether PVP-I nasal instillation can suppress mucosal inflammation in non-eosinophilic chronic rhinosinusitis (CRS) mice. This study aimed to explore the anti-inflammatory effects and underlying molecular mechanism of PVP-I on lipopolysaccharide-stimulated airway epithelial cells and investigate whether nasal instillation of PVP-I can suppress mucosal inflammation in non-eosinophilic CRS mice. Inflammation-related molecules in the nasal epithelial cells and non-eosinophilic CRS mice were measured by enzyme-linked immunosorbent assay, western blotting, quantitative real-time polymerase chain reaction, immunoprecipitation, and histopathological analysis. PVP-I blocked expressions of various inflammation-related molecules, such as NLRP3, NF-κB-p65, caspase-1, and IL-1β. Translocation of NF-κB to the nucleus, and assembly of NLRP3/ASC complexes in the nasal epithelial cells and non-eosinophilic CRS mice were also restricted. Notably, PVP-I strongly blocked the receptor co-localization of TLR4 and MyD88 in the epithelial cells of nasal mucosa. We demonstrated that PVP-I significantly attenuated inflammatory molecules and cytokines via blocking the formation of TLR4 and MyD88 complexes during LPS-induced mucosal inflammation in non-eosinophilic CRS.

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“…It is believed that Natterins have a substantial role as effector defense molecules. Their ability to activate cells and cytoplasmic multiprotein complexes that drive the host innate immune response might be due to the fact that all Natterin-like proteins have pore-forming domains and are generally classified as part of the aerolysin superfamily [ 3 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Natterin-like depletion by CRISPR/Cas9 impairs zebrafish (Danio rerio) embryonic development

et al. 2022

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Background The Natterin protein family was first discovered in the venom of the medically significant fish Thalassophryne nattereri, and over the last decade natterin-like genes have been identified in various organisms, notably performing immune-related functions. Previous findings support natterin-like genes as effector defense molecules able to activate multiprotein complexes driving the host innate immune response, notably due to the pore-forming function of the aerolysin superfamily members. Herein, employing a combination of the CRISPR/Cas9 depletion system, phenotype-based screening, and morphometric methods, we evaluated the role of one family member, LOC795232, in the embryonic development of zebrafish since it might be implicated in multiple roles and characterization of the null mutant is central for analysis of gene activity. Results Multiple sequence alignment revealed that the candidate natterin-like has the highest similarity to zebrafish aep1, a putative and better characterized fish-specific defense molecule from the same family. Compared to other species, zebrafish have many natterin-like copies. Whole-mount in situ hybridization confirmed the knockout and mutant embryos exhibited epiboly delay, growth retardation, yolk sac and heart edema, absent or diminished swim bladder, spinal defects, small eyes and head, heart dysfunction, and behavioral impairment. As previously demonstrated, ribonucleoproteins composed of Cas9 and duplex guide RNAs are effective at inducing mutations in the F0 zebrafish. Conclusions The considerably high natterin-like copies in zebrafish compared to other species might be due to the teleost-specific whole genome duplication and followed by subfunctionalization or neofunctionalization. In the present work, we described some of the natterin-like features in the zebrafish development and infer that natterin-like proteins potentially contribute to the embryonary development and immune response.

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Natterin an aerolysin-like fish toxin drives IL-1β-dependent neutrophilic inflammation mediated by caspase-1 and caspase-11 activated by the inflammasome sensor NLRP6

Cited by 15 publications

References 73 publications

The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function

The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function

Povidone iodine suppresses LPS-induced inflammation by inhibiting TLR4/MyD88 formation in airway epithelial cells

Natterin-like depletion by CRISPR/Cas9 impairs zebrafish (Danio rerio) embryonic development

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