Amin Zakeri - Academia.edu (original) (raw)
Papers by Amin Zakeri
Frontiers in Immunology
There is a strong correlation between dysregulation of the gastrointestinal microbiota and develo... more There is a strong correlation between dysregulation of the gastrointestinal microbiota and development of allergic diseases. The most prevalent therapies for relieving asthma symptoms are associated with serious side effects, and therefore novel approaches are needed. Our objective was to elucidate whether oral administration of Lactobacillus rhamnosus GG (LGG) as a probiotic or turmeric powder (TP) as a prebiotic or both as a synbiotic mitigate allergic inflammation including lung function, airway inflammatory cell infiltration, Th2 cytokines/chemokine in a murine model of house dust mite (HDM)induced asthma. BALB/c mice were intranasally sensitized and challenged with HDM received TP (20 mg/Kg mouse), or/and LGG (10 5 or 10 7 cfu/ml), or both orally. Interestingly, the synbiotic intervention (HDM-TP-LGG E7) specifically suppress the developement of airway hyperresponsiveness in response to methacholine. Besides, our synbiotic, TP, and LGG strongly down-regulated eosinophilia, IL-5, CCL17, IL-13. In terms of T cell response, CD4 + Th2 cells and CD4 + Th17 population were reduced in the splenocytes of the treatment groups compared to control. The synbiotic group not only elevated CD25 + Foxp3 + Treg frequency compared to asthmatic group, but also increased T reg cells compared to the probiotic group. The synbiotic also indicated the superior effect in suppressing Th2 cells compared to probiotic. Although, TP and LGG alone displayed suppressive effects, this study showed that the combination therapy consisting of TP and LGG (synbiotic) is more effective in some of the parameters than either of the treatments alone. This novel synbiotic, might be considered as a potential food-based drug for translational medicine and can possibly be used along with corticosteroid treatment.
Molecular Immunology
Consumption of fermentable dietary fibres, such as inulin, or administration of helminth products... more Consumption of fermentable dietary fibres, such as inulin, or administration of helminth products (e.g. Trichuris suis ova) have independently been shown to alleviate inflammation in vivo. We recently found that dietary inulin and T. suis infection in pigs co-operatively suppressed type-1 inflammatory responses in the gut, suggesting the potential of dietary components to augment anti-inflammatory responses induced by certain helminths. Here, we explored whether T. suis antigens and inulin could directly suppress inflammatory responses in vitro in a cooperative manner. T. suis soluble products (TsSP) strongly suppressed lipopolysaccharide (LPS)-induced IL-6 and TNF-α secretion from murine macrophages and induced an anti-inflammatory phenotype as evidenced by transcriptomic and gene pathway analyses. Inulin regulated the expression of a small number of genes and transcriptional pathways in macrophages after exposure to LPS, but did not enhance the suppressive activity of TsSP, either directly or in co-culture experiments with intestinal epithelial cells. Culture of macrophages with short-chain fatty acids, the products of microbial fermentation of inulin, did however appear to enhance TsSP-mediated inhibition of TNF-α production. Our results confirm a direct role for helminth products in suppressing inflammatory responses in macrophages. In contrast, inulin had little capacity to directly modulate LPS-induced responses. Our results suggest distinct mode-of-actions of T. suis and inulin in regulating inflammatory responses, and that the role of inulin in modulating the response to helminth infection may be dependent on other factors such as production of metabolites by the gut microbiota.
Frontiers in Immunology
Helminth parasites are masters at manipulating host immune responses, using an array of sophistic... more Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to establish chronic infections is the targeting of pattern recognition receptors (PRRs) including toll-like receptors, C-type lectin receptors, and the inflammasome. Given the critical role of these receptors and their intracellular pathways in regulating innate inflammatory responses, and also directing adaptive immunity toward Th1 and Th2 responses, recognition of the pathways triggered and/or modulated by helminths and their products will provide detailed insights about how helminths are able to establish an immunoregulatory environment. However, helminths also target PRRs-independent mechanisms (and most likely other yet unknown mechanisms and pathways) underpinning the battery of different molecules helminths produce. Herein, the current knowledge on intracellular pathways in antigen presenting cells activated by helminth-derived biomolecules is reviewed. Furthermore, we discuss the importance of helminth-derived vesicles as a less-appreciated components released during infection, their role in activating these host intracellular pathways, and their implication in the development of new therapeutic approaches for inflammatory diseases and the possibility of designing a new generation of vaccines.
Frontiers in Immunology
Asthma is a chronic airway inflammatory disease that is influenced by the interplay between genet... more Asthma is a chronic airway inflammatory disease that is influenced by the interplay between genetic factors and exposure to environmental allergens, microbes, or microbial products where toll-like receptors (TLRs) play a pivotal role. TLRs recognize a wide range of microbial or endogenous molecules as well as airborne environmental allergens and act as adjuvants that influence positively or negatively allergic sensitization. TLRs are qualitatively and differentially expressed on hematopoietic and non-hematopoietic stromal or structural airway cells that when activated by TLRs agonists exert an immune-modulatory role in asthma development. Therefore, understanding mechanisms and pathways by which TLRs orchestrate asthma outcomes may offer new strategies to control the disease. Here, we aim to review and critically discuss the role of TLRs in human asthma and murine models of allergic airway inflammation, highlighting the complexity of TLRs function in development, exacerbation, or control of airway allergic inflammation.
The Clinical Respiratory Journal
Borji et al. have recently published a Letter to the Editor in response to the previous critical ... more Borji et al. have recently published a Letter to the Editor in response to the previous critical letter on their original paper in The Clinical Respiratory Journal. This commentary letter aims to criticize their response letter via indicating to important notes which seem to have been ignored by Borji and colleagues. The main flawed that their original paper suffers from is lack of credible assay showing whether their helminth-derived antigens are contaminated with LPS. In fact, there is no reliable study concerning immunoregulatory functions of helminths in which the evaluation of LPS contamination in helminth antigens has been neglected. However, Borji et al in their response letter attempt to justify this significant deficiency and strictly disclaim the probability of LPS contamination in their helminth-derived antigens via indicating to an irrelevant unpublished data. To clarify, in the previous letter, it has been indicated to the presence of LPS in the abomasum of sheep, not the existence of live bacteria (resident bacteria) in this organ. In addition, contamination of worms and their cuticle with rumen fluids containing a huge amount of gram negative bacteria and LPS during collecting abomasums from abattoir is an indispensable matter. Thus, it appears that these factors have quite been disregarded by Borji and colleagues. Regarding their unpublished data, the authors state “in order to investigate the level of LPS contamination ES product of M. marshalli, we studied the effect of this antigen on gene expression of TLR4 on asthmatic and non-asthmatic mouse”. But, it should be taken into account that this is absolutely an unreliable and irrelevant approach to obtain the precise level of LPS in helminth-derived antigens. In support of this, high dose of LPS can suppress TLR4 expression and signalling in immune cells, indicating that no reliable conclusion concerning LPS dose is provided by evaluation of TLR4 expression. Importantly, there is no scientific and valid document to approve such a method for LPS measurement. Thus, it seems that no reasonable explanation has been expressed by Borji et al. to support the accuracy of results in their research paper. Surprisingly, in the last section of Response letter, the authors cite to their recent paper (related to the results of a PhD thesis) to underpin the regulatory effects of M. marshalli antigens by indicating ‘cytokine profile’, while there are no supporting results in this article regarding cytokine profile confirming immunoregulation in asthmatic mice. The results of cytokine profile are significantly different from what Borji and colleagues claim on immunoregulation. Finally, Borji et al. declare that ‘writing of some data in the manuscript is optional’, but it should be noted that in all scientific papers the data to which the authors indicate in the context should be supported by convincing evidence such as protocols, techniques, figures and graphs either in supplementary file or in the body of paper, otherwise this will undoubtedly create ambiguity making questions for readers. Furthermore, the authors have still not provided persuasive data such as graphs (proliferation assay, negative control) and methods (for distinguishing different types of asthmatic patients) in their response letter to corroborate their explanations.
Parasitology
SUMMARY During microbial infections, both innate and adaptive immunity are activated. Viruses and... more SUMMARY During microbial infections, both innate and adaptive immunity are activated. Viruses and bacteria usually induce an acute inflammation in the first setting of infection, which helps the eliciting an effective immune response. In contrast, macroparasites such as helminths are a highly successful group of invaders known to be capable of maintaining a chronic infestation with the minimum instigation. Undoubtedly, generating such an immunoregulatory environment requires the exploitation of various immunosuppressive mechanisms to debilitate host immunity supporting their survival and replication. Several mechanisms have been recognized whereby helminths prolong their infections including an increase of immunoregulatory cells, inhibition of Th1 or Th2 responses, targeting pattern recognition receptors (PRRs) and lowering the immune cells quantity via induction of apoptosis. Apoptosis is a programmed intracellular process involving a series of consecutive downstream signalling eve...
Biochimica et Biophysica Acta (BBA) - General Subjects, 2016
BACKGROUND Innate immune cells as the first line of defense are adept at recognizing and triggeri... more BACKGROUND Innate immune cells as the first line of defense are adept at recognizing and triggering appropriate response against various pathogens. Apart from the protective functions, the innate immunity plays an essential role in mediation of allergic responses. Dendritic cells (DCs) and airway epithelial cells (AECs) along with other innate cells such as granulocytes, natural killer cells (NKs), natural killer T cells (NKTs), and alternatively activated macrophages (AAMs) are able to orchestrate allergic responses, especially asthma. Chronic stimulation of TLRs by airway stimuli induces local inflammation which gradually results in the recruitment and settling of innate cells around airways. SCOPE OF REVIEW This review discusses how recruitment and accumulation of the inflammatory cells in the site of insult facilitate hypersensitivity reactions and initiate airway inflammation. We indicate that these cells are well equipped to highly sensitive receptors known as toll-like receptors (TLRs) making them fit to prime adaptive immune response. Based on emerging findings, we highlight the pivotal role of TLRs in regulation of innate cells function in the context of asthma disease. MAJOR CONCLUSIONS Stimulation of the TLRs of innate cells by allergens has been found to accelerate and regulate allergic airway inflammation. In fact, the sophisticated interaction between environmental allergens and TLRs leads to release of various pro-inflammatory mediators from innate cells supporting asthma development. GENERAL SIGNIFICANCE This review highlights that TLRs have a substantial role in priming innate cells and cytokine release, suggesting that the involvement of TLRs of innate immune cells can modulate the function of these cells in asthma disease.
Current Bionanotechnology, 2016
International Reviews of Immunology, 2016
Toll-like receptors (TLRs) are essential components of the innate immune system. They play an imp... more Toll-like receptors (TLRs) are essential components of the innate immune system. They play an important role in the pathogenesis of allergic diseases, especially asthma. Since TLRs significantly orchestrate innate and adaptive immune response, their manipulation has widely been considered as a potential approach to control asthma symptoms. It is well established that helminths have immunoregulatory effects on host immune responses, especially innate immunity. They release bioactive molecules such as excretory-secretory (ES) products manipulating TLRs expression and signaling. Thus, given the promising results derived from preclinical studies, harnessing helminth-derived molecules affecting TLRs can be considered as a potential biological therapy for allergic diseases. Prospectively, the data that are available at present suggest that, in the near future, it is possible that helminth antigens will offer new therapeutic strategies and druggable targets for fighting allergic diseases. This review describes the interactions between helminths and TLRs and discusses the potential possibilities for asthma therapy. In this opinion paper, the authors aimed to review the updated literatures on the interplay between helminths, TLRs, and asthma with a view to proposing helminth-based asthma therapy.
The Clinical Respiratory Journal, 2015
Journal of Extracellular Vesicles
Frontiers in Immunology
There is a strong correlation between dysregulation of the gastrointestinal microbiota and develo... more There is a strong correlation between dysregulation of the gastrointestinal microbiota and development of allergic diseases. The most prevalent therapies for relieving asthma symptoms are associated with serious side effects, and therefore novel approaches are needed. Our objective was to elucidate whether oral administration of Lactobacillus rhamnosus GG (LGG) as a probiotic or turmeric powder (TP) as a prebiotic or both as a synbiotic mitigate allergic inflammation including lung function, airway inflammatory cell infiltration, Th2 cytokines/chemokine in a murine model of house dust mite (HDM)induced asthma. BALB/c mice were intranasally sensitized and challenged with HDM received TP (20 mg/Kg mouse), or/and LGG (10 5 or 10 7 cfu/ml), or both orally. Interestingly, the synbiotic intervention (HDM-TP-LGG E7) specifically suppress the developement of airway hyperresponsiveness in response to methacholine. Besides, our synbiotic, TP, and LGG strongly down-regulated eosinophilia, IL-5, CCL17, IL-13. In terms of T cell response, CD4 + Th2 cells and CD4 + Th17 population were reduced in the splenocytes of the treatment groups compared to control. The synbiotic group not only elevated CD25 + Foxp3 + Treg frequency compared to asthmatic group, but also increased T reg cells compared to the probiotic group. The synbiotic also indicated the superior effect in suppressing Th2 cells compared to probiotic. Although, TP and LGG alone displayed suppressive effects, this study showed that the combination therapy consisting of TP and LGG (synbiotic) is more effective in some of the parameters than either of the treatments alone. This novel synbiotic, might be considered as a potential food-based drug for translational medicine and can possibly be used along with corticosteroid treatment.
Molecular Immunology
Consumption of fermentable dietary fibres, such as inulin, or administration of helminth products... more Consumption of fermentable dietary fibres, such as inulin, or administration of helminth products (e.g. Trichuris suis ova) have independently been shown to alleviate inflammation in vivo. We recently found that dietary inulin and T. suis infection in pigs co-operatively suppressed type-1 inflammatory responses in the gut, suggesting the potential of dietary components to augment anti-inflammatory responses induced by certain helminths. Here, we explored whether T. suis antigens and inulin could directly suppress inflammatory responses in vitro in a cooperative manner. T. suis soluble products (TsSP) strongly suppressed lipopolysaccharide (LPS)-induced IL-6 and TNF-α secretion from murine macrophages and induced an anti-inflammatory phenotype as evidenced by transcriptomic and gene pathway analyses. Inulin regulated the expression of a small number of genes and transcriptional pathways in macrophages after exposure to LPS, but did not enhance the suppressive activity of TsSP, either directly or in co-culture experiments with intestinal epithelial cells. Culture of macrophages with short-chain fatty acids, the products of microbial fermentation of inulin, did however appear to enhance TsSP-mediated inhibition of TNF-α production. Our results confirm a direct role for helminth products in suppressing inflammatory responses in macrophages. In contrast, inulin had little capacity to directly modulate LPS-induced responses. Our results suggest distinct mode-of-actions of T. suis and inulin in regulating inflammatory responses, and that the role of inulin in modulating the response to helminth infection may be dependent on other factors such as production of metabolites by the gut microbiota.
Frontiers in Immunology
Helminth parasites are masters at manipulating host immune responses, using an array of sophistic... more Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to establish chronic infections is the targeting of pattern recognition receptors (PRRs) including toll-like receptors, C-type lectin receptors, and the inflammasome. Given the critical role of these receptors and their intracellular pathways in regulating innate inflammatory responses, and also directing adaptive immunity toward Th1 and Th2 responses, recognition of the pathways triggered and/or modulated by helminths and their products will provide detailed insights about how helminths are able to establish an immunoregulatory environment. However, helminths also target PRRs-independent mechanisms (and most likely other yet unknown mechanisms and pathways) underpinning the battery of different molecules helminths produce. Herein, the current knowledge on intracellular pathways in antigen presenting cells activated by helminth-derived biomolecules is reviewed. Furthermore, we discuss the importance of helminth-derived vesicles as a less-appreciated components released during infection, their role in activating these host intracellular pathways, and their implication in the development of new therapeutic approaches for inflammatory diseases and the possibility of designing a new generation of vaccines.
Frontiers in Immunology
Asthma is a chronic airway inflammatory disease that is influenced by the interplay between genet... more Asthma is a chronic airway inflammatory disease that is influenced by the interplay between genetic factors and exposure to environmental allergens, microbes, or microbial products where toll-like receptors (TLRs) play a pivotal role. TLRs recognize a wide range of microbial or endogenous molecules as well as airborne environmental allergens and act as adjuvants that influence positively or negatively allergic sensitization. TLRs are qualitatively and differentially expressed on hematopoietic and non-hematopoietic stromal or structural airway cells that when activated by TLRs agonists exert an immune-modulatory role in asthma development. Therefore, understanding mechanisms and pathways by which TLRs orchestrate asthma outcomes may offer new strategies to control the disease. Here, we aim to review and critically discuss the role of TLRs in human asthma and murine models of allergic airway inflammation, highlighting the complexity of TLRs function in development, exacerbation, or control of airway allergic inflammation.
The Clinical Respiratory Journal
Borji et al. have recently published a Letter to the Editor in response to the previous critical ... more Borji et al. have recently published a Letter to the Editor in response to the previous critical letter on their original paper in The Clinical Respiratory Journal. This commentary letter aims to criticize their response letter via indicating to important notes which seem to have been ignored by Borji and colleagues. The main flawed that their original paper suffers from is lack of credible assay showing whether their helminth-derived antigens are contaminated with LPS. In fact, there is no reliable study concerning immunoregulatory functions of helminths in which the evaluation of LPS contamination in helminth antigens has been neglected. However, Borji et al in their response letter attempt to justify this significant deficiency and strictly disclaim the probability of LPS contamination in their helminth-derived antigens via indicating to an irrelevant unpublished data. To clarify, in the previous letter, it has been indicated to the presence of LPS in the abomasum of sheep, not the existence of live bacteria (resident bacteria) in this organ. In addition, contamination of worms and their cuticle with rumen fluids containing a huge amount of gram negative bacteria and LPS during collecting abomasums from abattoir is an indispensable matter. Thus, it appears that these factors have quite been disregarded by Borji and colleagues. Regarding their unpublished data, the authors state “in order to investigate the level of LPS contamination ES product of M. marshalli, we studied the effect of this antigen on gene expression of TLR4 on asthmatic and non-asthmatic mouse”. But, it should be taken into account that this is absolutely an unreliable and irrelevant approach to obtain the precise level of LPS in helminth-derived antigens. In support of this, high dose of LPS can suppress TLR4 expression and signalling in immune cells, indicating that no reliable conclusion concerning LPS dose is provided by evaluation of TLR4 expression. Importantly, there is no scientific and valid document to approve such a method for LPS measurement. Thus, it seems that no reasonable explanation has been expressed by Borji et al. to support the accuracy of results in their research paper. Surprisingly, in the last section of Response letter, the authors cite to their recent paper (related to the results of a PhD thesis) to underpin the regulatory effects of M. marshalli antigens by indicating ‘cytokine profile’, while there are no supporting results in this article regarding cytokine profile confirming immunoregulation in asthmatic mice. The results of cytokine profile are significantly different from what Borji and colleagues claim on immunoregulation. Finally, Borji et al. declare that ‘writing of some data in the manuscript is optional’, but it should be noted that in all scientific papers the data to which the authors indicate in the context should be supported by convincing evidence such as protocols, techniques, figures and graphs either in supplementary file or in the body of paper, otherwise this will undoubtedly create ambiguity making questions for readers. Furthermore, the authors have still not provided persuasive data such as graphs (proliferation assay, negative control) and methods (for distinguishing different types of asthmatic patients) in their response letter to corroborate their explanations.
Parasitology
SUMMARY During microbial infections, both innate and adaptive immunity are activated. Viruses and... more SUMMARY During microbial infections, both innate and adaptive immunity are activated. Viruses and bacteria usually induce an acute inflammation in the first setting of infection, which helps the eliciting an effective immune response. In contrast, macroparasites such as helminths are a highly successful group of invaders known to be capable of maintaining a chronic infestation with the minimum instigation. Undoubtedly, generating such an immunoregulatory environment requires the exploitation of various immunosuppressive mechanisms to debilitate host immunity supporting their survival and replication. Several mechanisms have been recognized whereby helminths prolong their infections including an increase of immunoregulatory cells, inhibition of Th1 or Th2 responses, targeting pattern recognition receptors (PRRs) and lowering the immune cells quantity via induction of apoptosis. Apoptosis is a programmed intracellular process involving a series of consecutive downstream signalling eve...
Biochimica et Biophysica Acta (BBA) - General Subjects, 2016
BACKGROUND Innate immune cells as the first line of defense are adept at recognizing and triggeri... more BACKGROUND Innate immune cells as the first line of defense are adept at recognizing and triggering appropriate response against various pathogens. Apart from the protective functions, the innate immunity plays an essential role in mediation of allergic responses. Dendritic cells (DCs) and airway epithelial cells (AECs) along with other innate cells such as granulocytes, natural killer cells (NKs), natural killer T cells (NKTs), and alternatively activated macrophages (AAMs) are able to orchestrate allergic responses, especially asthma. Chronic stimulation of TLRs by airway stimuli induces local inflammation which gradually results in the recruitment and settling of innate cells around airways. SCOPE OF REVIEW This review discusses how recruitment and accumulation of the inflammatory cells in the site of insult facilitate hypersensitivity reactions and initiate airway inflammation. We indicate that these cells are well equipped to highly sensitive receptors known as toll-like receptors (TLRs) making them fit to prime adaptive immune response. Based on emerging findings, we highlight the pivotal role of TLRs in regulation of innate cells function in the context of asthma disease. MAJOR CONCLUSIONS Stimulation of the TLRs of innate cells by allergens has been found to accelerate and regulate allergic airway inflammation. In fact, the sophisticated interaction between environmental allergens and TLRs leads to release of various pro-inflammatory mediators from innate cells supporting asthma development. GENERAL SIGNIFICANCE This review highlights that TLRs have a substantial role in priming innate cells and cytokine release, suggesting that the involvement of TLRs of innate immune cells can modulate the function of these cells in asthma disease.
Current Bionanotechnology, 2016
International Reviews of Immunology, 2016
Toll-like receptors (TLRs) are essential components of the innate immune system. They play an imp... more Toll-like receptors (TLRs) are essential components of the innate immune system. They play an important role in the pathogenesis of allergic diseases, especially asthma. Since TLRs significantly orchestrate innate and adaptive immune response, their manipulation has widely been considered as a potential approach to control asthma symptoms. It is well established that helminths have immunoregulatory effects on host immune responses, especially innate immunity. They release bioactive molecules such as excretory-secretory (ES) products manipulating TLRs expression and signaling. Thus, given the promising results derived from preclinical studies, harnessing helminth-derived molecules affecting TLRs can be considered as a potential biological therapy for allergic diseases. Prospectively, the data that are available at present suggest that, in the near future, it is possible that helminth antigens will offer new therapeutic strategies and druggable targets for fighting allergic diseases. This review describes the interactions between helminths and TLRs and discusses the potential possibilities for asthma therapy. In this opinion paper, the authors aimed to review the updated literatures on the interplay between helminths, TLRs, and asthma with a view to proposing helminth-based asthma therapy.
The Clinical Respiratory Journal, 2015
Journal of Extracellular Vesicles