- Email: [email protected]
Teaching Shrimps Self-Defense to Fight Infections
TIBTEC 1654 No. of Pages 4
Forum
Teaching Shrimps Self-Defense to Fight Infections
impose major yield-limiting effects on production, causing significant losses [5]. To avoid production losses, several veterinary drugs are commonly used. However, their imprudent use has resulted in the development of antimicrobial resistance Parisa Norouzitallab,1,2,4,* (AMR) in many shrimp pathogens (includKartik Baruah,2,3,4 ing bacteria, fungi, viruses, and parasites). Daisy Vanrompay,1,5 and Consequently, veterinary drugs are no Peter Bossier2,5 longer effective in treating shrimp disA paradigm shift in our under- eases in some cases. An alternative standing of shrimp immunity offers approach to combat diseases could be to train the defense system of shrimps the potential to develop novel disagainst microbial attacks.
ease-control strategies. We summarize cutting-edge findings on the phenomenon of trained immunity in shrimps and discuss how it may contribute to new avenues for controlling disease in these aquaculturally important animals. Shrimp Diseases: An Obstacle to Sustainable Production
Training the Defense System of Shrimps Invertebrate shrimps do not possess a specific immune system like that of vertebrates. To fight infections, they rely solely on their innate immune responses, which are generally characterized as rapid (hours to days), nonspecific, and without the development of immunological memory. Interestingly, however, a few studies on insects as model organisms indicated that the invertebrate innate immune system could be educated to mount enhanced and enduring protective immune responses against both related and unrelated pathogens [6,7]. These claims of trained immunity in invertebrates were based largely on the observations that prior exposure to a primary infection and/or immune elicitors increased the efficacy of the immune system or enhanced the resistance of the animals against secondary infections [6]. In those studies, the effects of innate immune memory appeared to persist over a longer time span, reaching almost the lifetime of the individual, or sometimes across generations [6,7]. This capacity of innate immunity to react in an adaptive manner to secondary challenges represents a memory-like characteristic of innate immunity called ‘trained immunity’.
The world population is projected to exceed 9 billion by 2050. Food consumption per capita and the demand for animal proteins are also expected to increase considerably [1]: overall agricultural production will need to increase by about 70% to meet the projected demand. Animal husbandry alone will not be able to meet the demand, so there is a dire need for sustainable sources that could contribute to world’s future food security and nutrition [2]. Some candidates are invertebrate sources including insects [3], but crustacean shrimps (Penaeus vannamei, Penaeus monodon) currently represent a protein source that is more culturally palatable in many parts of the world. Additionally, shrimps already represent a significant portion of aquaculture products, with a global production of around 4.88 million metric tons representing a value of about US$39 billion [4]. The expansion of farmed shrimps, however, is not without major issues. Infectious The emerging view that innate immunity diseases such as acute hepatopancreatic could be trained was examined in necrosis disease and white gut disease shrimps, with the aim of developing a
more predictable, reliable, cost-effective, and ultimately more sustainable diseasecontrol strategy. The results of a transgenerational study using the shrimp model organism Artemia suggested that training induced by exposing the parental population of Artemia at their early life stages to challenge with Vibrio campbellii (an important shrimp bacterial pathogen) significantly increased the resistance of the three succeeding generations of progeny (of which none was exposed to the parental stressor) against subsequent challenge with the same bacterial strain (Figure 1) [8]. A subsequent study used a similar experimental approach (Figure 1) to elucidate whether training with another stimulus, nonlethal heat shock (NLHS) (37 C), would similarly induce protective responses in Artemia. NLHS is a classical stress inducer that was previously shown to improve resistance against infection stress in a single generation of Artemia through the induction of heat shock protein 70 (Hsp70) [9]. On early exposure to daily NLHSs, a parental population of Artemia experienced an increase in Hsp70 levels, which was associated with improved resistance towards subsequent pathogenic V. campbellii challenge. Interestingly, these acquired phenotypic traits were inherited by three successive, unexposed generations [10]. Observations of the development of trained immunity are particular interesting in longlived cultured penaeid shrimps. So far, no study has investigated the phenomenon of trained immunity by performing a transgenerational experiment. However, experimental studies conducted in a single generation of shrimps suggested that trained immunity effects could last for a relatively long period of up to 50 days (see a recent review [11] and references therein). For example, training P. monodon with DNA vaccines encoding the envelope proteins VP28 and VP281 (VP36B) Trends in Biotechnology, Month Year, Vol. xx, No. yy
1
TIBTEC 1654 No. of Pages 4
Brine shrimp cyst (F0)
Brine shrimp decapsulated cyst (F0)
Brine shrimp larvae (F0)
Training induced by exposure to V. campbellii/nonlethal heat stress (T-F0)
No training, reared under normal condiƟons (C-F0)
Treatment was terminated once the animals were at juvenile stage (T-F0)
No training, reared under normal condiƟons (C-F0)
Animals were reared under normal condiƟons to adult (T-F0)
Animals were reared under normal condiƟons to adult (C-F0) No exposure to V. campbellii/nonlethal heat stress
Cyst (T-F1)
Larvae (C-F1) were not used
Larvae (T-F1) were not used
Cyst (C-F1)
Cyst (C-F1) decapsulated
Cyst (T-F1) decapsulated
Larvae (T-F1) Larvae (C-F1) High resistance Larvae (T-F2)
Larvae (T-F3)
Low resistance Larvae (C-F2)
Larvae (C-F3)
(See figure legend on the bottom of the next page.)
2
Trends in Biotechnology, Month Year, Vol. xx, No. yy
EpigeneƟc modificaƟons on immune genes
TIBTEC 1654 No. of Pages 4
Priming the immune system (bioƟc or abioƟc)
Immune primed Naive
period of up to 3 weeks after vaccination ([11] and references therein). In another study on P. vannamei, training induced by exposing the shrimp to chronic NLHS (at 38 C for 5 min every day for 7 days) markedly increased the shrimps’ tolerance to Vibrio parahaemolyticus-caused acute hepatopancreatic necrosis disease [12].
Mechanisms Underpinning Trained Immunity
Immune gene expression
The mechanisms underpinning trained immunity in shrimps remain unclear. Immune challenge Immune primed However, based on the reports that epigenetic regulatory mechanisms, such as DNA methylation and histone modifications, are central elements in regulating appropriately the expression of immune Naive, challenged genes [13], epigenetic programming at specific immune-related loci is likely to be involved in the mechanisms leading Naive, non-challenged to trained immunity. Following these groundbreaking findings, another study Time (during the challenge) (Figure 2) [8] investigated the underlying molecular bases. The inheritance of the acquired resistance phenotype was assoFigure 2. Schematic Presentation of How Immune Gene Expression Is Regulated through Epigenetic Marks during an Immune Challenge. Trained immunity is associated with coordinated ciated with elevated levels of the immune reprogramming of innate immune gene expression through epigenetic modifications. During an immune signaling molecules Hsp70 and high challenge, initial activation of gene transcription is accompanied by the rapid acquisition of specific chromatin mobility group box 1, alteration in the marks, which may be partially lost after elimination of the original stimulus [14]. The presence of the geneexpression of selected innate immunityregulating epigenetic marks maintains the genes at the primed stage and results in a stronger response to reinfection. Although many of these epigenetic marks will be erased during gametogenesis, the most essential related genes, and a stochastic pattern in genes keep their epigenetic marks during this process and pass unchanged from parents to progeny through the global acetylation level of H4 and trithe mechanism of a self-sustaining feedback loop. However, these epigenetic marks will also be erased after a methylation level of H3K4 histones in the few generations in the absence of the initial stimulus. progenies whose ancestors were trained by Vibrio exposure. protected the shrimp from subsequent postlarvae (PL18) by immersing the PL in infection with a pathogenic white spot syn- a vaccine bath containing heat-killed and Concluding Remarks and Future drome virus for a period of up to 50 days formalin-inactivated Vibrio harveyi ‘vac- Directions after intramuscular injection with the vac- cines’ induced increased resistance on Taken together, recent studies provide cine. Similarly, vaccinating P. monodon challenge with V. harveyi for a prolonged the first indications for the hypothesis that
Time
Figure 1. Schematic Representation of the Concept of Trained Immunity. The effect of trained immunity on shrimp disease resistance was determined using the brine shrimp Artemia as a model organism. Brine shrimp cysts (dormant embryos) were used to produce the parental generation. To avoid any possible microbial contamination from the previous environment, the brine shrimp cysts were hatched under axenic (germ-free) conditions as described previously [8,10]. On hatching, the F0 progeny were divided into two groups. One group was exposed to a nonlethal heat stress (a classical stress inducer) or the pathogenic bacterium Vibrio campbellii ahead of the reproductive period (T-F0). The other group was grown unexposed, under normal culture conditions (C-F0). Approximately 28 days post-hatching, the parental (F0) females from the treatment (T-F0) and control (C-F0) groups produced their next-generation cysts (i.e., T-F1 and C-F1, respectively). The disinfected cysts were hatched to produce their corresponding larvae (i.e., T-F1 and C-F1). The F1 larvae from both groups were further cultured isothermally at 28 C, without stress exposure, to maturity, after which the F2 larvae were collected. The experiment was continued until, and including, the F3 generation. The T-F1 to T-F3 progenies from both groups were tested for their resistance phenotypes by conducting stress resistance tests. Training induced by exposure of the parental generation to an abiotic/ biotic stressor markedly increased the resistance of the T-F1 to T-F3 progenies towards secondary infection. Adapted, with permission, from [8,10].
Trends in Biotechnology, Month Year, Vol. xx, No. yy
3
TIBTEC 1654 No. of Pages 4
trained immunity is present in cultured shrimps and can contribute to fighting against disease. Shrimps can be trained by pre-exposing them to various stimuli, such as nonlethal thermal stress or microbes. Training immunity can be an additional approach to fight disease and this new concept, on better characterization of the functional details, could both redefine the function of the innate immune system and aid in designing new drugs to control diseases challenging these highvalue food organisms. While the recent findings have provided much information, much remains to be learned in this new field of immunology over the coming years. Future efforts should focus on the molecular mechanisms that mediate trained immunity, with more indepth understanding at the immunological, metabolic, and epigenetic levels. In an aquaculture setting, NLHS may not be the best stimulus to induce trained immunity in crustaceans because acute temperature shifts could be detrimental, adversely affecting physiological and immunological balance and causing significant mortality. Another crucial direction for research is to
4
Trends in Biotechnology, Month Year, Vol. xx, No. yy
develop training agents that could noninvasively induce trained immunity in shrimps and protect the animals against subsequent microbial infection. Finally, the concept of trained immunity should be explored to design novel prophylactic and therapeutic approaches. 1
3. van Huis, A. et al. (2013) Edible Insects: Future Prospects for Food and Feed Security: FAO Forestry Paper 171, Food and Agriculture Organization of the United Nations 4. FAO (2016) The State of World Fisheries and Aquaculture 2016. Contributing to Food Security and Nutrition for All, Food and Agriculture Organization of the United Nations 5. Stentiford, G.D. et al. (2017) New paradigms to help solve the global aquaculture disease crisis. PLoS Pathog. 13, e1006160 6. Kurtz, J. and Franz, K. (2003) Evidence for memory in invertebrate immunity. Nature 425, 37–38
Laboratory of Immunology and Animal Biotechnology, Department of Animal Sciences and Aquatic Ecology,
7. Little, T.J. et al. (2005) Invertebrate immunity and the limits of mechanistic immunology. Nat. Immunol. 6, 651–654
Ghent University, Coupure links 653, Ghent 9000, Belgium 2 Laboratory of Aquaculture & Artemia Reference Center, Department of Animal Sciences and Aquatic Ecology, Faculty of Bioscience Engineering, Coupure links 653, Ghent 9000, Belgium
8. Norouzitallab, P. et al. (2016) Probing the phenomenon of trained immunity in invertebrates during a transgenerational study, using brine shrimp Artemia as a model system. Sci. Rep. 6, 21166
3
Department of Animal Nutrition and Management, Faculty of Veterinary Medicine and Animal Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden 4 These authors contributed equally to this Forum 5 Daisy Vanrompay and Peter Bossier have contributed equally as senior authors *Correspondence: [email protected] (P. Norouzitallab). https://doi.org/10.1016/j.tibtech.2018.05.007 References 1. Cai, J. and Leung, P.S. (2017) Short-Term Projection of Global Fish Demand and Supply Gaps: FAO Fisheries and Aquaculture Technical Paper T607, Food and Agriculture Organization of the United Nations 2. Golden, C. et al. (2016) Fall in fish catch threatens human health. Nature 534, 317–320
9. Norouzitallab, P. et al. (2015) Non-lethal heat shock induces HSP70 and HMGB1 protein production sequentially to protect Artemia franciscana against Vibrio campbellii. Fish Shellfish Immunol. 42, 395–399 10. Norouzitallab, P. et al. (2014) Environmental heat stress induces epigenetic transgenerational inheritance of robustness in parthenogenetic Artemia model. FASEB J. 28, 3552–3563 11. Chang, Y.H. et al. (2018) What vaccination studies tell us about immunological memory within the innate immune system of cultured shrimp and crayfish. Dev. Comp. Immunol. 80, 53–66 12. Junprung, W. et al. (2017) HSP70 and HSP90 are involved in shrimp Penaeus vannamei tolerance to AHPND-causing strain of Vibrio parahaemolyticus after non-lethal heat shock. Fish Shellfish Immunol. 60, 237–246 13. Ma, M. and Ra, M. (2014) RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat. Rev. Genet. 15, 394–408 14. Netea, M.G. et al. (2016) Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098
Forum
Teaching Shrimps Self-Defense to Fight Infections
impose major yield-limiting effects on production, causing significant losses [5]. To avoid production losses, several veterinary drugs are commonly used. However, their imprudent use has resulted in the development of antimicrobial resistance Parisa Norouzitallab,1,2,4,* (AMR) in many shrimp pathogens (includKartik Baruah,2,3,4 ing bacteria, fungi, viruses, and parasites). Daisy Vanrompay,1,5 and Consequently, veterinary drugs are no Peter Bossier2,5 longer effective in treating shrimp disA paradigm shift in our under- eases in some cases. An alternative standing of shrimp immunity offers approach to combat diseases could be to train the defense system of shrimps the potential to develop novel disagainst microbial attacks.
ease-control strategies. We summarize cutting-edge findings on the phenomenon of trained immunity in shrimps and discuss how it may contribute to new avenues for controlling disease in these aquaculturally important animals. Shrimp Diseases: An Obstacle to Sustainable Production
Training the Defense System of Shrimps Invertebrate shrimps do not possess a specific immune system like that of vertebrates. To fight infections, they rely solely on their innate immune responses, which are generally characterized as rapid (hours to days), nonspecific, and without the development of immunological memory. Interestingly, however, a few studies on insects as model organisms indicated that the invertebrate innate immune system could be educated to mount enhanced and enduring protective immune responses against both related and unrelated pathogens [6,7]. These claims of trained immunity in invertebrates were based largely on the observations that prior exposure to a primary infection and/or immune elicitors increased the efficacy of the immune system or enhanced the resistance of the animals against secondary infections [6]. In those studies, the effects of innate immune memory appeared to persist over a longer time span, reaching almost the lifetime of the individual, or sometimes across generations [6,7]. This capacity of innate immunity to react in an adaptive manner to secondary challenges represents a memory-like characteristic of innate immunity called ‘trained immunity’.
The world population is projected to exceed 9 billion by 2050. Food consumption per capita and the demand for animal proteins are also expected to increase considerably [1]: overall agricultural production will need to increase by about 70% to meet the projected demand. Animal husbandry alone will not be able to meet the demand, so there is a dire need for sustainable sources that could contribute to world’s future food security and nutrition [2]. Some candidates are invertebrate sources including insects [3], but crustacean shrimps (Penaeus vannamei, Penaeus monodon) currently represent a protein source that is more culturally palatable in many parts of the world. Additionally, shrimps already represent a significant portion of aquaculture products, with a global production of around 4.88 million metric tons representing a value of about US$39 billion [4]. The expansion of farmed shrimps, however, is not without major issues. Infectious The emerging view that innate immunity diseases such as acute hepatopancreatic could be trained was examined in necrosis disease and white gut disease shrimps, with the aim of developing a
more predictable, reliable, cost-effective, and ultimately more sustainable diseasecontrol strategy. The results of a transgenerational study using the shrimp model organism Artemia suggested that training induced by exposing the parental population of Artemia at their early life stages to challenge with Vibrio campbellii (an important shrimp bacterial pathogen) significantly increased the resistance of the three succeeding generations of progeny (of which none was exposed to the parental stressor) against subsequent challenge with the same bacterial strain (Figure 1) [8]. A subsequent study used a similar experimental approach (Figure 1) to elucidate whether training with another stimulus, nonlethal heat shock (NLHS) (37 C), would similarly induce protective responses in Artemia. NLHS is a classical stress inducer that was previously shown to improve resistance against infection stress in a single generation of Artemia through the induction of heat shock protein 70 (Hsp70) [9]. On early exposure to daily NLHSs, a parental population of Artemia experienced an increase in Hsp70 levels, which was associated with improved resistance towards subsequent pathogenic V. campbellii challenge. Interestingly, these acquired phenotypic traits were inherited by three successive, unexposed generations [10]. Observations of the development of trained immunity are particular interesting in longlived cultured penaeid shrimps. So far, no study has investigated the phenomenon of trained immunity by performing a transgenerational experiment. However, experimental studies conducted in a single generation of shrimps suggested that trained immunity effects could last for a relatively long period of up to 50 days (see a recent review [11] and references therein). For example, training P. monodon with DNA vaccines encoding the envelope proteins VP28 and VP281 (VP36B) Trends in Biotechnology, Month Year, Vol. xx, No. yy
1
TIBTEC 1654 No. of Pages 4
Brine shrimp cyst (F0)
Brine shrimp decapsulated cyst (F0)
Brine shrimp larvae (F0)
Training induced by exposure to V. campbellii/nonlethal heat stress (T-F0)
No training, reared under normal condiƟons (C-F0)
Treatment was terminated once the animals were at juvenile stage (T-F0)
No training, reared under normal condiƟons (C-F0)
Animals were reared under normal condiƟons to adult (T-F0)
Animals were reared under normal condiƟons to adult (C-F0) No exposure to V. campbellii/nonlethal heat stress
Cyst (T-F1)
Larvae (C-F1) were not used
Larvae (T-F1) were not used
Cyst (C-F1)
Cyst (C-F1) decapsulated
Cyst (T-F1) decapsulated
Larvae (T-F1) Larvae (C-F1) High resistance Larvae (T-F2)
Larvae (T-F3)
Low resistance Larvae (C-F2)
Larvae (C-F3)
(See figure legend on the bottom of the next page.)
2
Trends in Biotechnology, Month Year, Vol. xx, No. yy
EpigeneƟc modificaƟons on immune genes
TIBTEC 1654 No. of Pages 4
Priming the immune system (bioƟc or abioƟc)
Immune primed Naive
period of up to 3 weeks after vaccination ([11] and references therein). In another study on P. vannamei, training induced by exposing the shrimp to chronic NLHS (at 38 C for 5 min every day for 7 days) markedly increased the shrimps’ tolerance to Vibrio parahaemolyticus-caused acute hepatopancreatic necrosis disease [12].
Mechanisms Underpinning Trained Immunity
Immune gene expression
The mechanisms underpinning trained immunity in shrimps remain unclear. Immune challenge Immune primed However, based on the reports that epigenetic regulatory mechanisms, such as DNA methylation and histone modifications, are central elements in regulating appropriately the expression of immune Naive, challenged genes [13], epigenetic programming at specific immune-related loci is likely to be involved in the mechanisms leading Naive, non-challenged to trained immunity. Following these groundbreaking findings, another study Time (during the challenge) (Figure 2) [8] investigated the underlying molecular bases. The inheritance of the acquired resistance phenotype was assoFigure 2. Schematic Presentation of How Immune Gene Expression Is Regulated through Epigenetic Marks during an Immune Challenge. Trained immunity is associated with coordinated ciated with elevated levels of the immune reprogramming of innate immune gene expression through epigenetic modifications. During an immune signaling molecules Hsp70 and high challenge, initial activation of gene transcription is accompanied by the rapid acquisition of specific chromatin mobility group box 1, alteration in the marks, which may be partially lost after elimination of the original stimulus [14]. The presence of the geneexpression of selected innate immunityregulating epigenetic marks maintains the genes at the primed stage and results in a stronger response to reinfection. Although many of these epigenetic marks will be erased during gametogenesis, the most essential related genes, and a stochastic pattern in genes keep their epigenetic marks during this process and pass unchanged from parents to progeny through the global acetylation level of H4 and trithe mechanism of a self-sustaining feedback loop. However, these epigenetic marks will also be erased after a methylation level of H3K4 histones in the few generations in the absence of the initial stimulus. progenies whose ancestors were trained by Vibrio exposure. protected the shrimp from subsequent postlarvae (PL18) by immersing the PL in infection with a pathogenic white spot syn- a vaccine bath containing heat-killed and Concluding Remarks and Future drome virus for a period of up to 50 days formalin-inactivated Vibrio harveyi ‘vac- Directions after intramuscular injection with the vac- cines’ induced increased resistance on Taken together, recent studies provide cine. Similarly, vaccinating P. monodon challenge with V. harveyi for a prolonged the first indications for the hypothesis that
Time
Figure 1. Schematic Representation of the Concept of Trained Immunity. The effect of trained immunity on shrimp disease resistance was determined using the brine shrimp Artemia as a model organism. Brine shrimp cysts (dormant embryos) were used to produce the parental generation. To avoid any possible microbial contamination from the previous environment, the brine shrimp cysts were hatched under axenic (germ-free) conditions as described previously [8,10]. On hatching, the F0 progeny were divided into two groups. One group was exposed to a nonlethal heat stress (a classical stress inducer) or the pathogenic bacterium Vibrio campbellii ahead of the reproductive period (T-F0). The other group was grown unexposed, under normal culture conditions (C-F0). Approximately 28 days post-hatching, the parental (F0) females from the treatment (T-F0) and control (C-F0) groups produced their next-generation cysts (i.e., T-F1 and C-F1, respectively). The disinfected cysts were hatched to produce their corresponding larvae (i.e., T-F1 and C-F1). The F1 larvae from both groups were further cultured isothermally at 28 C, without stress exposure, to maturity, after which the F2 larvae were collected. The experiment was continued until, and including, the F3 generation. The T-F1 to T-F3 progenies from both groups were tested for their resistance phenotypes by conducting stress resistance tests. Training induced by exposure of the parental generation to an abiotic/ biotic stressor markedly increased the resistance of the T-F1 to T-F3 progenies towards secondary infection. Adapted, with permission, from [8,10].
Trends in Biotechnology, Month Year, Vol. xx, No. yy
3
TIBTEC 1654 No. of Pages 4
trained immunity is present in cultured shrimps and can contribute to fighting against disease. Shrimps can be trained by pre-exposing them to various stimuli, such as nonlethal thermal stress or microbes. Training immunity can be an additional approach to fight disease and this new concept, on better characterization of the functional details, could both redefine the function of the innate immune system and aid in designing new drugs to control diseases challenging these highvalue food organisms. While the recent findings have provided much information, much remains to be learned in this new field of immunology over the coming years. Future efforts should focus on the molecular mechanisms that mediate trained immunity, with more indepth understanding at the immunological, metabolic, and epigenetic levels. In an aquaculture setting, NLHS may not be the best stimulus to induce trained immunity in crustaceans because acute temperature shifts could be detrimental, adversely affecting physiological and immunological balance and causing significant mortality. Another crucial direction for research is to
4
Trends in Biotechnology, Month Year, Vol. xx, No. yy
develop training agents that could noninvasively induce trained immunity in shrimps and protect the animals against subsequent microbial infection. Finally, the concept of trained immunity should be explored to design novel prophylactic and therapeutic approaches. 1
3. van Huis, A. et al. (2013) Edible Insects: Future Prospects for Food and Feed Security: FAO Forestry Paper 171, Food and Agriculture Organization of the United Nations 4. FAO (2016) The State of World Fisheries and Aquaculture 2016. Contributing to Food Security and Nutrition for All, Food and Agriculture Organization of the United Nations 5. Stentiford, G.D. et al. (2017) New paradigms to help solve the global aquaculture disease crisis. PLoS Pathog. 13, e1006160 6. Kurtz, J. and Franz, K. (2003) Evidence for memory in invertebrate immunity. Nature 425, 37–38
Laboratory of Immunology and Animal Biotechnology, Department of Animal Sciences and Aquatic Ecology,
7. Little, T.J. et al. (2005) Invertebrate immunity and the limits of mechanistic immunology. Nat. Immunol. 6, 651–654
Ghent University, Coupure links 653, Ghent 9000, Belgium 2 Laboratory of Aquaculture & Artemia Reference Center, Department of Animal Sciences and Aquatic Ecology, Faculty of Bioscience Engineering, Coupure links 653, Ghent 9000, Belgium
8. Norouzitallab, P. et al. (2016) Probing the phenomenon of trained immunity in invertebrates during a transgenerational study, using brine shrimp Artemia as a model system. Sci. Rep. 6, 21166
3
Department of Animal Nutrition and Management, Faculty of Veterinary Medicine and Animal Sciences, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden 4 These authors contributed equally to this Forum 5 Daisy Vanrompay and Peter Bossier have contributed equally as senior authors *Correspondence: [email protected] (P. Norouzitallab). https://doi.org/10.1016/j.tibtech.2018.05.007 References 1. Cai, J. and Leung, P.S. (2017) Short-Term Projection of Global Fish Demand and Supply Gaps: FAO Fisheries and Aquaculture Technical Paper T607, Food and Agriculture Organization of the United Nations 2. Golden, C. et al. (2016) Fall in fish catch threatens human health. Nature 534, 317–320
9. Norouzitallab, P. et al. (2015) Non-lethal heat shock induces HSP70 and HMGB1 protein production sequentially to protect Artemia franciscana against Vibrio campbellii. Fish Shellfish Immunol. 42, 395–399 10. Norouzitallab, P. et al. (2014) Environmental heat stress induces epigenetic transgenerational inheritance of robustness in parthenogenetic Artemia model. FASEB J. 28, 3552–3563 11. Chang, Y.H. et al. (2018) What vaccination studies tell us about immunological memory within the innate immune system of cultured shrimp and crayfish. Dev. Comp. Immunol. 80, 53–66 12. Junprung, W. et al. (2017) HSP70 and HSP90 are involved in shrimp Penaeus vannamei tolerance to AHPND-causing strain of Vibrio parahaemolyticus after non-lethal heat shock. Fish Shellfish Immunol. 60, 237–246 13. Ma, M. and Ra, M. (2014) RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat. Rev. Genet. 15, 394–408 14. Netea, M.G. et al. (2016) Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098