Increased Susceptibility toYersinia enterocoliticaInfection ofTff2Deficient Mice

Shah, Aftab Ali; Mihalj, Martina; Ratkay, Ivana; Lubka-Pathak, Maria; Balogh, Péter; Klingel, Karin; Bohn, E.; Blin, Nikolaus; Baus-Lončar, Mirela

doi:10.1159/000341463

Cited by 12 publications

(14 citation statements)

References 38 publications

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“…The TFF domain is highly conserved in vertebrates, and TFFs harboring one to four TFF domains have been identified in species from frogs to humans (15)(16)(17). Several lines of evidence suggest possible roles for TFFs in the modulation of the host immune system (18,19), but the actions by which TFFs exert their biological activities are still largely unknown. It would be very interesting to investigate whether TFFs function via combination with partners, such as aerolysin-like proteins, from either the host or microbes to modulate host antimicrobial and immune responses in other vertebrate species, including mammals.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Xiang

Yan

Guo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

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Aerolysins are virulence factors belonging to the bacterial β-poreforming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.innate immunity | infectious disease | interleukin-1beta

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Section: Discussionmentioning

confidence: 99%

“…In particular, TFF2 has been shown to be essential in the regulation of IL-33 release at mucosal surfaces (18). Increased susceptibility to Yersinia enterocolitica was found in TFF2-knockout mice, which died following infection (19).…”

mentioning

confidence: 99%

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Xiang

Yan

Guo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

View full text Add to dashboard Cite

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“…3a). [17][18][19][20][21][22][23][24][25] On the other hand, the expression of genes coding for other markers of pulmonary epithelial cells (SCGB1A1, SP-A, (Table S2). Moreover, deficiency of NLRP3 or ASC did not reduce the expression of plasminogen activator inhibitor-1 (also known as SERPINE1), which has been reported to prevent severe lung injury after S. pneumoniae infection (Table S2).…”

Section: Asc-and Nlrp3-dependent Gene Expression In the Lungmentioning

confidence: 99%

“…The epithelial repair factor TFF2 has recently been implicated in host defense against microbial infections. 19,28 We examined the effect of TFF2, intelectin-1, and BPIFA1 on pneumococcal pneumonia. Pycard −/− mice were transfected intranasally with expression vectors for TFF2, intelectin-1, or BPIFA1 or an empty vector and then infected with S. pneumoniae.…”

Section: Asc-and Nlrp3-dependent Gene Expression In the Lungmentioning

confidence: 99%

ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism

et al. 2019

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It is widely accepted that inflammasomes protect the host from microbial pathogens by inducing inflammatory responses through caspase-1 activation. Here, we show that the inflammasome components ASC and NLRP3 are required for resistance to pneumococcal pneumonia, whereas caspase-1 and caspase-11 are dispensable. In the lung of S. pneumoniae-infected mice, ASC and NLRP3, but not caspase-1/11, were required for optimal expression of several mucosal innate immune proteins. Among them, TFF2 and intelectin-1 appeared to be protective against pneumococcal pneumonia. During infection, ASC and NLRP3 maintained the expression of the transcription factor SPDEF, which can facilitate the expression of the mucosal defense factor genes. Moreover, activation of STAT6, a key regulator of Spdef expression, depended on ASC and NLRP3. Overexpression of these inflammasome proteins sustained STAT6 phosphorylation induced by type 2 cytokines. Collectively, this study suggests that ASC and NLRP3 promote airway mucosal innate immunity by an inflammasome-independent mechanism involving the STAT6-SPDEF pathway.

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“…Tff2 KO mice had increased susceptibility to Helicobacter felis-induced gastritis (25), they showed accelerated progression of gastritis to dysplasia in the antrum (44), and laser-induced photodamage of the gastric surface epithelium resulted in an attenuated alkalization of the surface pH in these animals (45). Furthermore, Tff2 KO mice showed an altered expression of genes implicated in the immune system (46), they were hyperresponsive to interleukin-1β stimulation (25), exhibited increased susceptibility to Yersinia enterocolitica infection (47), and displayed reduced gut immunopathology after oral infection with Toxoplasma gondii (48). Taken together, TFF2 KO mice show both gastric and immunological phenotypes.…”

Section: Tff2 a Muc6-binding Lectin Stabilizing The Gastric Mucus Bamentioning

confidence: 99%

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

Hoffmann

2015

International Journal of Oncology

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Abstract. The peptide TFF2 (formerly 'spasmolytic polypeptide'), a member of the trefoil factor family (TFF) containing two TFF domains, is mainly expressed together with the mucin MUC6 in the gastric epithelium and duodenal Brunner's glands. Pathologically, TFF2 expression is observed ectopically during stone diseases, chronic inflammatory conditions and in several metaplastic and neoplastic epithelia; most prominent being the 'spasmolytic polypeptide-expressing metaplasia' (SPEM), which is an established gastric precancerous lesion. TFF2 plays a critical role in maintaining gastric mucosal integrity and appears to restrain tumorigenesis in the stomach. Recently, porcine TFF2 has been shown to interact with the gastric mucin MUC6 and thus stabilize the gastric mucus barrier. On the one hand, TFF2 binds to MUC6 via non-covalent lectin interactions with the glycotope GlcNAcα1→4Galβ1→R. On the other hand, TFF2 is probably also covalently bound to MUC6 via disulfide bridges. Thus, implications for the complex multimeric assembly, cross-linking, and packaging of MUC6 as well as the rheology of gastric mucus are discussed in detail in this review. Furthermore, TFF2 is also expressed in minor amounts in the immune and nervous systems. Thus, similar to galectins, its lectin activity would perfectly enable TFF2 to form multivalent complexes and cross-linked lattices with a plethora of transmembrane glycoproteins and thus modulate different signal transduction processes. This could explain the multiple and diverse biological effects of TFF2 [e.g., motogenic, (anti)apoptotic, and angiogenic effects]. Finally, a function during fertilization is also possible for TFF domains because they occur as shuffled modules in certain zona pellucida proteins.

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Increased Susceptibility toYersinia enterocoliticaInfection ofTff2Deficient Mice

Cited by 12 publications

References 38 publications

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

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