Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice

Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

doi:10.1016/j.vetpar.2016.07.009

Cited by 17 publications

(19 citation statements)

References 31 publications

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“…In our study, rFgTPx attached with high affinity to the surface of PBMCs, indicating that this protein may interact with immune cell surface receptors, thereby inducing immune response. F. gigantica is a helminth parasite that drives Th1/Th2 immune responses in its mammalian host [ 25 , 26 , 27 ]. F. gigantica discharges many ES molecules that seem to play roles in the induction of this type of immune response.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Functions of Goat Peripheral Blood Mononuclear Cells by Fasciola gigantica Thioredoxin Peroxidase In Vitro

Tian

Chen

et al. 2020

Pathogens

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The liver fluke Fasciola gigantica has a remarkable ability to establish a long-term infection within the hepatobiliary system of the mammalian definitive host. F. gigantica achieves this by producing excretory–secretory molecules, which have immunomodulatory activities. In an effort to elucidate the immunomodulatory functions of F. gigantica thioredoxin peroxidase protein (FgTPx), we expressed recombinant FgTPx (rFgTPx) in Escherichia coli bacteria and examined its effects on several functions of goat peripheral blood mononuclear cells (PBMCs) in vitro. Sequence analysis revealed that FgTPx is related to a thioredoxin-like superfamily. Western blot analysis showed that rFgTPx was recognized by the sera of goats experimentally infected by F. gigantica. The specific binding of rFgTPx protein to the surface of goat PBMCs was demonstrated by immunofluorescence staining. We investigated the influence of serial concentrations of rFgTPx on various functions of goat PBMCs. All concentrations of rFgTPx increased the secretion of interleukin-2 (IL-2), IL-4, IL-10, IL-17, transforming growth factor-beta (TGF-β), and interferon gamma (IFN-γ), but inhibited PBMC proliferation, migration, and monocyte phagocytosis. Goat PBMCs exposed to 20–40 μg/mL of rFgTPx secreted increased levels of nitric oxide (NO), and 10–40 μg/mL of rFgTPx promoted cell apoptosis. These findings indicate that rFgTPx influences various functions of goat PBMCs by interacting with a large number of cellular targets, ultimately to promote the parasite’s survival. The roles of rFgTPx and their interacting proteins warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Functions of Goat Peripheral Blood Mononuclear Cells by Fasciola gigantica Thioredoxin Peroxidase In Vitro

Tian

Chen

et al. 2020

Pathogens

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“…Cytokines are produced by a variety of leukocytes and play many roles in maintaining immune homeostasis in the host [ 25 , 26 ]. Fasciola gigantica infection can induce a mixed Th1/Th2 immune response [ 27 , 28 ]. Our evaluation of the cytokine production [Th1 (IFN-γ and IL-2) and Th2 (IL-4, IL-10 and TGF-β)] in PBMCs culture supernatants showed that rFgRab10 protein can induce both humoral and cellular immune responses, confirming an earlier observation [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fasciola gigantica infection can induce a mixed Th1/Th2 immune response [ 27 , 28 ]. Our evaluation of the cytokine production [Th1 (IFN-γ and IL-2) and Th2 (IL-4, IL-10 and TGF-β)] in PBMCs culture supernatants showed that rFgRab10 protein can induce both humoral and cellular immune responses, confirming an earlier observation [ 27 , 28 ]. Th1 cells secrete IFN-γ, which activates monocytes, thereby promoting the production of NO and phagocytosis [ 29 ], which may influence the development of the adaptive cellular immune response.…”

Section: Discussionmentioning

confidence: 99%

The pervasive effects of recombinant Fasciola gigantica Ras-related protein Rab10 on the functions of goat peripheral blood mononuclear cells

Tian

Zhang

et al. 2018

Parasites Vectors

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BackgroundFasciola gigantica-induced immunomodulation is a major hurdle faced by the host for controlling infection. Here, we elucidated the role of F. gigantica Ras-related protein Rab10 (FgRab10) in the modulation of key functions of peripheral blood mononuclear cells (PBMCs) of goats.MethodsWe cloned and expressed recombinant FgRab10 (rFgRab10) protein and examined its effects on several functions of goat PBMCs. Protein interactors of rFgRab10 were predicted in silico by querying the databases Intact, String, BioPlex and BioGrid. In addition, a total energy analysis of each of the identified interactions was also conducted. Gene Ontology (GO) enrichment analysis was carried out using FuncAssociate 3.0.ResultsThe FgRab10 gene (618 bp), encodes 205-amino-acid residues with a molecular mass of ~23 kDa, had complete nucleotide sequence homology with F. hepatica Ras family protein gene (PIS87503.1). The rFgRab10 protein specifically cross-reacted with anti-Fasciola antibodies as shown by Western blot and immunofluorescence analysis. This protein exhibited multiple effects on goat PBMCs, including increased production of cytokines [interleukin-2 (IL-2), IL-4, IL-10, transforming growth factor beta (TGF-β) and interferon gamma (IFN-γ)] and total nitric oxide (NO), enhancing apoptosis and migration of PBMCs, and promoting the phagocytic ability of monocytes. However, it significantly inhibited cell proliferation. Homology modelling revealed 63% identity between rFgRab10 and human Rab10 protein (Uniprot ID: P61026). Protein interaction network analysis revealed more stabilizing interactions between Rab proteins geranylgeranyltransferase component A 1 (CHM) and Rab proteins geranylgeranyltransferase component A 2 (CHML) and rFgRab10 protein. Gene Ontology analysis identified RabGTPase mediated signaling as the most represented pathway.ConclusionsrFgRab10 protein exerts profound influences on various functions of goat PBMCs. This finding may help explain why F. gigantica is capable of provoking recognition by host immune cells, less capable of destroying this successful parasite.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3148-2) contains supplementary material, which is available to authorized users.

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“…Fasciola hepatica infection in lambs can induce a dominant Th2-biased immune response along with suppression of Th1/Th17 responses [ 21 ] and can negatively impact Th1 responses to bystander infections, such as during coinfection with Mycobacterium tuberculosis [ 41 ]. Buffaloes, on the other hand, can exhibit a combination of Th1 and Th2 cytokine expression pattern in response to F. gigantica infection [ 42 , 43 ] or post vaccination with the recombinant fatty acid binding protein (rFABP) and glutathione S-transferase (rGST) protein [ 44 ]. Therefore, it is reasonable to expect some differences in the expression patterns of immune response genes that interact with or are stimulated in response to infection with F. gigantica and F. hepatica .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic responses of water buffalo liver to infection with the digenetic fluke Fasciola gigantica

Zhang

Elsheikha

et al. 2017

Parasites Vectors

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Background Fasciola gigantica, the tropical liver fluke, infects buffaloes in Asian and African countries and causes significant economic losses and poses public health threat in these countries. However, little is known of the transcriptional response of buffaloes to infection with F. gigantica. The objective of the present study was to perform the first transcriptomic analysis of buffalo liver infected by F. gigantica. Understanding the mechanisms that underpin F. gigantica infection in buffaloes will contribute to our ability to control this parasite.MethodsWe challenged buffaloes with 500 viable F. gigantica metacercariae and collected liver samples through a time course at 3, 42 and 70 days post-infection (dpi). Then, we performed gene expression analysis on liver samples using RNA sequencing (RNA-Seq) Illumina technology and confirmed the RNA-Seq data by quantitative RT-PCR analysis.ResultsTotals of 496, 880 and 441 differentially expressed transcripts were identified in the infected livers at 3, 42 and 70 dpi, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that transcriptional changes in the liver of infected buffaloes evolve over the course of infection. The predominant response of buffaloes to infection was mediated by certain pathways, such as MHC antigen processing and presentation, Toll-like receptor 4 (TLR4), transforming growth factor beta (TGF-β), and the cytochrome P450. Hepatic drug metabolizing enzymes and bile secretion were also affected.Conclusions Fasciola gigantica can induce statistically significant and biologically plausible differences in the hepatic gene expression of infected buffaloes. These findings provide new insights into the response of buffaloes to F. gigantica over the course of infection, which may be useful in determining pathways that can modulate host-parasite interaction and thus potentially important for clearance of the parasite.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-1990-2) contains supplementary material, which is available to authorized users.

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Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice

Cited by 17 publications

References 31 publications

Modulation of the Functions of Goat Peripheral Blood Mononuclear Cells by Fasciola gigantica Thioredoxin Peroxidase In Vitro

Modulation of the Functions of Goat Peripheral Blood Mononuclear Cells by Fasciola gigantica Thioredoxin Peroxidase In Vitro

The pervasive effects of recombinant Fasciola gigantica Ras-related protein Rab10 on the functions of goat peripheral blood mononuclear cells

Transcriptomic responses of water buffalo liver to infection with the digenetic fluke Fasciola gigantica

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