Full length articleLive Edwardsiella tarda vaccine enhances innate immunity by metabolic modulation in zebrafish
Graphical abstract
Introduction
Recently developed metabolomics is a high-throughput approach to detect and profile changes in metabolites which are the end products of cellular processes. It can discover the metabolic pathways which are linked to biological mechanisms, shape the understanding of medicines how to play an action and reprogram the metabolism by exogenous complementation [1]. Gas chromatography/mass spectrometry (GC/MS), liquid chromatography-mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR) are the three most used analytical technologies to investigate metabolic profiling [2]. Out of them, GC/MS has been widely used since it possesses three golden standards, high chromatographic resolution, very reproducible chromatography and searchable mass spectra libraries [3].
Immunometabolism is an emerging field at the interface between immune response and metabolism, showing how immune cells regulate metabolism and metabolic pathways regulates immune response outcome [4]. The multilevel interactions between the metabolic and immune systems promote our understanding of pathogenic mechanisms and offer substantial therapeutic promise. Investigation on immunometabolism has been reported in Drosophila melanogaster infected with Listeria monocytogenes, mice and human infected with Staphylococcus aureus, human infected with Mycobacterium tuberculosis using metabolomics approach [5], [6], [7]. Very recently, we have used the GC/MS based metabolomics identifies biomarkers that differentiate death from survival carps infected with Edwardsiella tarda [8]. We have demonstrated that crucial biomarkers identified by the metabolomics approach may elevate survival of tilapia and zebrafish infected with bacterial pathogens [9], [10], [11]. Furthermore, the developed functional metabolomics discloses an unknown mechanism of fatty acids by which IFN-α2b protects host from microbial infections [10]. These results indicate that investigation on metabolomics contributes to an understanding of immunological mechanisms and immune metabolic regulation.
Immunoprophylaxis is an effective measure to prevent and control infections [12]. Live vaccine, activated vaccine and subunit vaccine are three types of vaccines which have been widely used in the immunoprophylaxis. Gram-negative enteric pathogen E. tarda causes an infectious disease, called edwardsiellosis, in a wide range of hosts including fish, amphibians, reptiles and mammals [13], [14], [15], [16], [17]. This infection leads to serious economic losses and a threat to humans [18], [19]. Commercial vaccines against E. tarda are not available, although empirical vaccine candidate development strategy works well [20], [21], [22], [23]. Limited understanding of protective mechanisms of the experimental vaccines leads to an increased interest in exploring metabolic reconstruction by vaccines. The goal of the present study is to investigate metabolite profiling of zebrafish in response to live E. tarda vaccines for understanding vaccine mechanisms and identifying crucial metabolites that modulate innate immune response. The results obtained are reported as follows.
Section snippets
Bacterial strain, growth condition and vaccine preparation
E. tarda EIB202 was provided by Professor Yuanxing Zhang, East China University of Science and Technology. All chemicals were purchased from Sigma–Aldrich. Single colony of E. tarda EIB202 was picked from plate and propagated overnight in 5 mL tryptic soybroth (TSB) medium at 200 rpm (Sky-111B, SuKun, China) at 30 °C. Aliquot 1 mL culture was diluted into 1:100 using fresh TSB medium and grown at 30 °C. Bacterial cells were harvested at an OD600 of 1.0 by centrifugation at 6000 g (Universal
Protective efficiency of bacterial immunostimulation and metabolomics profiling of zebrafish humoral fluid
To identify the functional pathways and metabolites that were required for immunity after vaccination with live E. tarda, we investigated metabolomes of zebrafish exposed or not exposed to the bacterium as outlined in Fig. 1A. Zebrafish was infected by E. tarda and the resulting accumulating death showed that significant immune protection was found at p < 0.05 (Log-rank test) between the exposure and control (Fig. 1B). On the other hand, we collected humoral fluid at 48 h after these injections
Discussion
A line of evidences has demonstrated that vaccine induces not only adaptive immunity but also innate immunity [35]. Recently, regulation of metabolites to immunity has been reported [36]. Elevated crucial metabolites identified from a stress-related metabolome enhance the metabolome's ability against the stress such as bacterial infection [9]. The present study reveals that vaccine can mounts metabolic strategy to cope with microbial infection. This finding is also consistent with our recent
Acknowledgments
This work was sponsored by grants from Science and Technology Program of Guangzhou (201504010025), NSFC Projects (41276145, 31272702), “973” Project (2012CB114406), Doctoral Fund of Ministry of Education of China (20120171110008).
References (48)
Extending the breadth of metabolite profiling by gas chromatography coupled to mass spectrometry
Trends Anal. Chem.
(2008)- et al.
Metabolic pathways in immune cell activation and quiescence
Immunity
(2013) - et al.
New sputum metabolite markers implicating adaptations of the host to Mycobacterium tuberculosis, and vice versa
Tuberculosis (Edinb)
(2013) - et al.
GC/MS-based metabolomics approach to identify biomarkers differentiating survivals from death in crucian carps infected by Edwardsiella tarda
Fish. Shellfish Immunol.
(2014) - et al.
N-acetylglucosamine enhances survival ability of tilapias infected by Streptococcus iniae
Fish. Shellfish Immunol.
(2014) - et al.
Liver functional metabolomics discloses an action of l-leucine against Streptococcus iniae infection in tilapias
Fish. Shellfish Immunol.
(2015) - et al.
Edwardsiella tarda invasion of fish cell lines and the activation of divergent cell death pathways
Vet. Microbiol.
(2013) - et al.
Multi-locus Sequence Analysis (MLSA) of Edwardsiella tarda isolates from fish
Vet. Microbiol.
(2012) - et al.
Analysis of the vaccine potential of a natural avirulent Edwardsiella tarda isolate
Vaccine
(2010) - et al.
Gene expression profiling in live attenuated Edwardsiella tarda vaccine immunized and challenged zebrafish: insights into the basic mechanisms of protection seen in immunized fish
Dev. Comp. Immunol.
(2013)
Identification of protective immunogens from extracellular secretome of Edwardsiella tarda
Fish. Shellfish Immunol.
Amphioxus CaVPT and creatine kinase are crucial immune-related molecules in response to bacterial infection and immunization
Fish. Shellfish Immunol.
L-proline increases survival of tilapias infected by Streptococcus agalactiae in higher water temperature
Fish. Shellfish Immunol.
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Immunity
Protective effect of lysozyme-galactomannan or lysozyme-palmitic acid conjugates against Edwardsiella tarda infection in carp, Cyprinus carpio L
FEBS Lett.
Notable mucosal immune responses induced in the intestine of zebrafish (Danio rerio) bath-vaccinated with a live attenuated Vibrio anguillarum vaccine
Fish. Shellfish Immunol.
Responses of Mytilus galloprovincialis to bacterial challenges by metabolomics and proteomics
Fish. Shellfish Immunol.
A manganese superoxide dismutase with potent antioxidant activity identified from Oplegnathus fasciatus: genomic structure and transcriptional characterization
Fish. Shellfish Immunol.
Mitochondrial peroxiredoxin 3 (Prx3) from rock bream (Oplegnathus fasciatus): immune responses and role of recombinant Prx3 in protecting cells from hydrogen peroxide induced oxidative stress
Fish. Shellfish Immunol.
Functional metabolomics: from biomarker discovery to metabolome reprogramming
Protein Cell
New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era
Chem. Rev.
Listeria monocytogenes infection causes metabolic shifts in Drosophila melanogaster
PLoS One
Metabolic profiling for detection of Staphylococcus aureus infection and antibiotic resistance
PLoS One
Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids
J. Proteome Res.
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The first two authors are equally contributed.