Transforming growth factor β (CiTGF-β) gene expression is induced in the inflammatory reaction of Ciona intestinalis

Vizzini, Aiti; Falco, Felicia Di; Parrinello, Daniela; Sanfratello, Maria Antonietta; Cammarata, Matteo

doi:10.1016/j.dci.2015.10.013

Cited by 31 publications

(17 citation statements)

References 44 publications

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“…This is contrary to what was observed in BCG-immunized animals. This cytokine has been shown to be up-regulated in inflammatory processes against bacterial infections 33 . Furthermore, TGF-β has also been implicated in the inhibition of mycobacterial growth 34 .…”

Section: Discussionmentioning

confidence: 99%

Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

Nascimento

Rodríguez

Santos

et al. 2017

Sci Rep

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In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.

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Section: Discussionmentioning

confidence: 99%

Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

Nascimento

Rodríguez

Santos

et al. 2017

Sci Rep

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“…These analyses demonstrated that, during the LPS-induced inflammation, Ascidians reprogram the expression of a CAP protein leading to the overexpression of a short variant with structural features largely different from the original one. In addition, it is noteworthy that, during LPS-induced inflammation, flowing haemocytes present a prompt activation of the transcription of other effector and regulatory molecules, such as galectins, a proPO-system and cytokines (CiTNF, CiIL-17s, CiTGF), Parrinello et al, 2010;Vizzini et al, 2016;Vizzini et al, 2015a;Vizzini et al, 2012;Vizzini et al, 2015c;Vizzini et al, 2008) demonstrating the importance of these cells during innate immune response.…”

Section: Discussionmentioning

confidence: 99%

“…They are proto-chordates with an innate immune system, including inflammatory humoral and cellular responses. An inflammatory response induced by LPS injection in the body wall of C. intestinalis is a well-established model for analysing regulator and effector inducible host defence molecules of the innate immune system, as shown for a type IX collagen-like , CAP-like (Bonura et al, 2010), MBL-like (Bonura et al, 2009), TNF␣-like Parrinello et al, 2010), galectin-like (Vizzini et al, 2012), peroxinectin (Vizzini et al, 2013a), Interleukins 17 (Vizzini et al, 2015a), the proPO-system Vizzini et al, 2015b) and TGF-␤ (Vizzini et al, 2016). In addition, our group described the first LPS-induced APA mechanism in this species with an intronic polyadenylation signal within the first intron leading to the upregulation of a short variant (Ci8 short) of an annotated mRNA and the modification of the tissue localization of this transcript (Vizzini et al, 2013a).…”

Section: Introductionmentioning

confidence: 99%

LPS injection reprograms the expression and the 3′ UTR of a CAP gene by alternative polyadenylation and the formation of a GAIT element in Ciona intestinalis

Vizzini¹,

Bonura

Longo

et al. 2016

Molecular Immunology

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a b s t r a c tThe diversification of cellular functions is one of the major characteristics of multicellular organisms which allow cells to modulate their gene expression, leading to the formation of transcripts and proteins with different functions and concentrations in response to different stimuli. CAP genes represent a widespread family of proteins belonging to the cysteine-rich secretory protein, antigen 5 and pathogenesis-related 1 superfamily which, it has been proposed, play key roles in the infection process and the modulation of immune responses in host animals. The ascidian Ciona intestinalis represents a group of proto-chordates with an exclusively innate immune system that has been widely studied in the field of comparative and developmental immunology. Using this biological system, we describe the identification of a novel APA mechanism by which an intronic polyadenylation signal is activated by LPS injection, leading to the formation of a shorter CAP mRNA capable of expressing the first CAP exon plus 19 amino acid residues whose sequence is contained within the first intron of the annotated gene. Furthermore, such an APA event causes the expression of a translational controlling cis-acting GAIT element which is not present in the previously isolated CAP isoform and identified in the 3 -UTR of other immunerelated genes, suggesting an intriguing scenario in which both transcriptional and post-transcriptional control mechanisms are involved in the activation of the CAP gene during inflammatory response in C. intestinalis.

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“…They are proto-chordates which possess an innate immune system, including inflammatory humoral and cellular responses. An inflammatory response induced by LPS injection in the body wall of C. intestinalis is a well-established model for the analysis of regulator and effector inducible host defense molecules of the innate immune system (Bonura et al, 2009;Parrinello et al, 2008Parrinello et al, , 2010Vizzini et al, 2012Vizzini et al, , 20132015a, 2015b2016). In the present paper, we report on the identification, characterization and expression of C. intestinalis g-type lysozymes.…”

Section: Introductionmentioning

confidence: 95%

Molecular characterisation, evolution and expression analysis of g-type lysozymes in Ciona intestinalis

Falco

Cammarata

Vizzini

2017

Developmental & Comparative Immunology

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a b s t r a c tLysozyme is an important defense molecule of the innate immune system. Known for its bactericidal properties, lysozyme catalyzes the hydrolysis of b-(1,4)-glycosidic bonds between the N-acetyl glucosamine and N-acetyl muramic acid in the peptidoglycan layer of bacterial cell walls. In this study, the complete coding sequence of four g-type lysozymes were identified in Ciona intestinalis. Phylogenetic analysis and modelling supported the hypothesis of a close relationship with the vertebrate g-type lysozymes suggesting that the C. intestinalis g-type lysozyme genes (CiLys-g1, Cilys-g2, CiLys-g3, CiLys-g4) share a common ancestor in the chordate lineage. Protein motif searches indicated that C. intestinalis gtype lysozymes contain a GEWL domain with a GXXQ signature, typical of goose lysozymes. Quantitative Real-Time PCR analysis results showed that transcripts are expressed in various tissues from C. intestinalis. In order to determine the involvement of C. intestinalis g-type lysozymes in immunity, their expression was analyzed in the pharynx, showing that transcripts were significantly up-regulated in response to a challenge with lipopolysaccharide (LPS). These data support the view that CiLys g-type are molecules with potential for immune defense system against bacterial infection.

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Transforming growth factor β (CiTGF-β) gene expression is induced in the inflammatory reaction of Ciona intestinalis

Cited by 31 publications

References 44 publications

Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

LPS injection reprograms the expression and the 3′ UTR of a CAP gene by alternative polyadenylation and the formation of a GAIT element in Ciona intestinalis

Molecular characterisation, evolution and expression analysis of g-type lysozymes in Ciona intestinalis

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