Yahya Sohrabi | Academy of Sciences of the Czech Republic (original) (raw)

Papers by Yahya Sohrabi

Atherosclerosis, Aug 1, 2019

Conclusion: In summary, our data demonstrate that mTOR dependent ROS production controls the oxLD... more Conclusion: In summary, our data demonstrate that mTOR dependent ROS production controls the oxLDL-induced trained innate immunity phenotype in human monocyte derived macrophages. Pharmacologic modulation of these pathways might provide a potential approach to modulate inflammation, associated with aberrant monocyte activation, during atherosclerosis development.

Frontiers in Immunology

Leishmaniasis, a disease caused by parasites of Leishmania spp., endangers more than 1 billion pe... more Leishmaniasis, a disease caused by parasites of Leishmania spp., endangers more than 1 billion people living in endemic countries and has three clinical forms: cutaneous, mucocutaneous, and visceral. Understanding of individual differences in susceptibility to infection and heterogeneity of its pathology is largely lacking. Different mouse strains show a broad and heterogeneous range of disease manifestations such as skin lesions, splenomegaly, hepatomegaly, and increased serum levels of immunoglobulin E and several cytokines. Genome-wide mapping of these strain differences detected more than 30 quantitative trait loci (QTLs) that control the response to Leishmania major. Some control different combinations of disease manifestations, but the nature of this heterogeneity is not yet clear. In this study, we analyzed the L. major response locus Lmr15 originally mapped in the strain CcS-9 which carries 12.5% of the genome of the resistant strain STS on the genetic background of the susc...

Med, Apr 1, 2021

Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there ... more Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there is an urgent need to reduce COVID-19 morbidity and mortality in elderly individuals. We discuss evidence suggesting that trained immunity elicited by BCG vaccination may improve immune responses and can serve as a strategy to combat COVID-19 in this population.

Cellular & Molecular Immunology

Clinical and Translational Medicine

Signal Transduction and Targeted Therapy

International Journal of Molecular Sciences

Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic ... more Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic inflammatory memory called trained innate immunity. Here, we have analyzed the role of the Liver X receptor (LXR), a crucial regulator of metabolism and inflammation, in oxidized low-density lipoprotein (oxLDL)-induced trained innate immunity. Human monocytes were incubated with LXR agonists, antagonists, and oxLDL for 24 h. After five days of resting time, cells were restimulated with the TLR-2 agonist Pam3cys. OxLDL priming induced the expression of LXRα but not LXRβ. Pharmacologic LXR activation was enhanced, while LXR inhibition prevented the oxLDL-induced inflammatory response. Furthermore, LXR inhibition blocked the metabolic changes necessary for epigenetic reprogramming associated with trained immunity. In fact, enrichment of activating histone marks at the IL-6 and TNFα promotor was reduced following LXR inhibition. Based on the differential expression of the LXR isoforms, we in...

PLoS Neglected Tropical Diseases, 2013

Background: L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although th... more Background: L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the recombinant congenic strain CcS-16 carrying 12.5% genes from the resistant parental strain STS/A and 87.5% genes from the susceptible strain BALB/c is more susceptible to L. tropica than BALB/c. We used these strains to map and functionally characterize the gene-loci regulating the immune responses and pathology. Methods: We analyzed genetics of response to L. tropica in infected F 2 hybrids between BALB/c6CcS-16. CcS-16 strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F 2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.

PLOS Neglected Tropical Diseases, 2022

Leishmaniasis continues to be a major health problem worldwide. The efficacy of reported vaccines... more Leishmaniasis continues to be a major health problem worldwide. The efficacy of reported vaccines is poor, and there is no safe and cost-effective treatment, partly because the mechanisms of the disease are not fully understood. RAU : PleasecheckwhethertheeditstothesentenceRecentstudiesha ecent studies have shed light on the role of interferon (IAU : PleasenotethattheabbreviationIFNhasbeenintroducedforinterferoninthesentenceRecentstudiesha FN)-inducible GTPases as regulators of immunity to infection. Farias Amorim and colleagues [1] describe differences in the transcriptome of blood cells isolated from patients infected with Leishmania braziliensis and healthy controls. They highlighted IFNγ and cytolytic transcriptional signatures characteristic for this cutaneous leishmaniasis. Their findings included overexpression of genes encoding guanylate-binding proteins (GBPs): GBP1, GBP2, GBP3, GBP4, GBP5, and GBP6 and the pseudogene GBP1P1. All detected GBPs except GBP2 were positively correlated with cell type abundance scores for monocytes and macrophage/ monocyte-like cells using the microenvironment cell population counter. However, the complexity of GBPs involvement in anti-Leishmania responses deserves additional attention.

Frontiers in Immunology

Differences in frequencies of blood cell subpopulations were reported to influence the course of ... more Differences in frequencies of blood cell subpopulations were reported to influence the course of infections, atopic and autoimmune diseases, and cancer. We have discovered a unique mouse strain B10.O20 containing extremely high frequency of myeloid-derived cells (MDC) in spleen. B10.O20 carries 3.6% of genes of the strain O20 on the C57BL/10 genetic background. It contains much higher frequency of CD11b+Gr1+ cells in spleen than both its parents. B10.O20 carries O20-derived segments on chromosomes 1, 15, 17, and 18. Their linkage with frequencies of blood cell subpopulations in spleen was tested in F2 hybrids between B10.O20 and C57BL/10. We found 3 novel loci controlling MDC frequencies: Mydc1, 2, and 3 on chromosomes 1, 15, and 17, respectively, and a locus controlling relative spleen weight (Rsw1) that co-localizes with Mydc3 and also influences proportion of white and red pulp in spleen. Mydc1 controls numbers of CD11b+Gr1+ cells. Interaction of Mydc2 and Mydc3 regulates frequen...

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishman... more Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. There are three major clinical forms of leishmaniasis: cutaneous, mucocutaneous and visceral. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis caused by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe, effective and affordable drug and vaccine against L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infecti...

Trends in Endocrinology & Metabolism

Trends in Molecular Medicine

Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there ... more Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there is an urgent need to reduce COVID-19 morbidity and mortality in elderly individuals. We discuss evidence suggesting that trained immunity elicited by BCG vaccination may improve immune responses and can serve as a strategy to combat COVID-19 in this population.

... et al . Genetic immunization with gp63 DNA results in a helper T cell type 1 immune response ... more ... et al . Genetic immunization with gp63 DNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis; ashemi-Fesharaki R, Ale-Agha S, Habbibi GR, et al . Production of inactivated ...

European Heart Journal

On behalf of Yamanashi Kawasaki Disease Research Group Introduction: Kawasaki disease (KD) is an ... more On behalf of Yamanashi Kawasaki Disease Research Group Introduction: Kawasaki disease (KD) is an acute systemic vasculitis in children associated with increased inflammatory cytokines and immune-regulatory abnormalities. While the underlying cause of KD is unknown, the pathomechanism of KD involves a complex multicellular dysfunction of mononuclear cells such as CD14+CD16+ activated monocytes, T-helper type 17 (Th17) cells, and regulatory T (Treg) cells. In recent years, plasma exchange (PE) is effective treatment for KD patients refractory to IVIG at acute phase. The mechanism of PE was reported to directly remove the plasma levels of cytokines from the blood circulation. But the effect of PE on immune cells remains unknown. Purpose: To further investigate the mechanism of action of PE, we examined changes in the abundance of activated monocytes, Treg cells, and Th17 cells in KD patients following treatment with PE. Methods: This study included fourteen children who were treated with PE for IVIG-resistant KD at University Hospital. The mean age was 28 months (range: 4-90 months). Daily PE was performed for three consecutive days. We obtained the peripheral blood samples before and after PE and measured total leukocyte counts, fractional counts of leukocyte. We also measured the absolute counts of CD14+CD16+ monocytes, Treg cells and Th17 cells by flow cytometry, and serum levels of soluble IL-2 receptor, IL-6, and TNF-α by enzyme-linked immunosorbent assay. Results: Absolute white blood cell counts decreased significantly after PE. But the percentage of monocytes, lymphocytes and some subclasses of white blood cells, including CD3+, CD4+, CD8+ T cells, and CD19+ B cells were no significant difference between before and after PE. However, the percentage of CD14+CD16+ monocytes in white blood cells, and the percentage of CD14+CD16+ monocytes in total CD14+ monocytes all significantly decrease after PE (1.1±1.5 vs. 2.1±2.3%, p<0.05; 20.0±18.7 vs. 26.1±21.1%, p<0.05). The percentage of Th17 cells in white blood cells and Th17 cells in CD4+ T cells were not significantly changed after PE (0.4±0.4 vs. 0.3±0.4%; 2.7±2.7 vs. 2.0±2.0%). But the percentage of Treg cells in white blood cells and Treg cells in CD4+ T cells both significantly increased after PE (1.8±0.9 vs. 0.9±0.6%, p<0.01; 11.1±5.1 vs. 8.0±4.4%, p<0.05). Plasma concentrations of soluble IL-2 receptor, IL-6 decreased significantly after PE (1003±495 vs. 2118±631 U/mL, p<0.01; 8.8±8.5 vs. 139.8±159.3 pg/mL, p<0.01). However, the plasma concentration of TNF-α was not significantly changed after PE (5.4±3.6 vs. 7.5±6.1 pg/mL). Conclusion: In these results, the mechanisms of PE to heal the inflammation were related to decrease the ratio of activated CD14+CD16+ monocytes to white blood cells. Furthermore, PE increased the ratio of Treg to white blood cells and improve the Treg/Th17 cell imbalance in KD. P3795 2-arachidonoylglycerol activates pro-inflammatory pathways in murine macrophages and promotes atherogenesis in ApoE-/-mice

Atherosclerosis, Aug 1, 2019

Conclusion: In summary, our data demonstrate that mTOR dependent ROS production controls the oxLD... more Conclusion: In summary, our data demonstrate that mTOR dependent ROS production controls the oxLDL-induced trained innate immunity phenotype in human monocyte derived macrophages. Pharmacologic modulation of these pathways might provide a potential approach to modulate inflammation, associated with aberrant monocyte activation, during atherosclerosis development.

Frontiers in Immunology

Leishmaniasis, a disease caused by parasites of Leishmania spp., endangers more than 1 billion pe... more Leishmaniasis, a disease caused by parasites of Leishmania spp., endangers more than 1 billion people living in endemic countries and has three clinical forms: cutaneous, mucocutaneous, and visceral. Understanding of individual differences in susceptibility to infection and heterogeneity of its pathology is largely lacking. Different mouse strains show a broad and heterogeneous range of disease manifestations such as skin lesions, splenomegaly, hepatomegaly, and increased serum levels of immunoglobulin E and several cytokines. Genome-wide mapping of these strain differences detected more than 30 quantitative trait loci (QTLs) that control the response to Leishmania major. Some control different combinations of disease manifestations, but the nature of this heterogeneity is not yet clear. In this study, we analyzed the L. major response locus Lmr15 originally mapped in the strain CcS-9 which carries 12.5% of the genome of the resistant strain STS on the genetic background of the susc...

Med, Apr 1, 2021

Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there ... more Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there is an urgent need to reduce COVID-19 morbidity and mortality in elderly individuals. We discuss evidence suggesting that trained immunity elicited by BCG vaccination may improve immune responses and can serve as a strategy to combat COVID-19 in this population.

Cellular & Molecular Immunology

Clinical and Translational Medicine

Signal Transduction and Targeted Therapy

International Journal of Molecular Sciences

Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic ... more Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic inflammatory memory called trained innate immunity. Here, we have analyzed the role of the Liver X receptor (LXR), a crucial regulator of metabolism and inflammation, in oxidized low-density lipoprotein (oxLDL)-induced trained innate immunity. Human monocytes were incubated with LXR agonists, antagonists, and oxLDL for 24 h. After five days of resting time, cells were restimulated with the TLR-2 agonist Pam3cys. OxLDL priming induced the expression of LXRα but not LXRβ. Pharmacologic LXR activation was enhanced, while LXR inhibition prevented the oxLDL-induced inflammatory response. Furthermore, LXR inhibition blocked the metabolic changes necessary for epigenetic reprogramming associated with trained immunity. In fact, enrichment of activating histone marks at the IL-6 and TNFα promotor was reduced following LXR inhibition. Based on the differential expression of the LXR isoforms, we in...

PLoS Neglected Tropical Diseases, 2013

Background: L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although th... more Background: L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the recombinant congenic strain CcS-16 carrying 12.5% genes from the resistant parental strain STS/A and 87.5% genes from the susceptible strain BALB/c is more susceptible to L. tropica than BALB/c. We used these strains to map and functionally characterize the gene-loci regulating the immune responses and pathology. Methods: We analyzed genetics of response to L. tropica in infected F 2 hybrids between BALB/c6CcS-16. CcS-16 strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F 2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.

PLOS Neglected Tropical Diseases, 2022

Leishmaniasis continues to be a major health problem worldwide. The efficacy of reported vaccines... more Leishmaniasis continues to be a major health problem worldwide. The efficacy of reported vaccines is poor, and there is no safe and cost-effective treatment, partly because the mechanisms of the disease are not fully understood. RAU : PleasecheckwhethertheeditstothesentenceRecentstudiesha ecent studies have shed light on the role of interferon (IAU : PleasenotethattheabbreviationIFNhasbeenintroducedforinterferoninthesentenceRecentstudiesha FN)-inducible GTPases as regulators of immunity to infection. Farias Amorim and colleagues [1] describe differences in the transcriptome of blood cells isolated from patients infected with Leishmania braziliensis and healthy controls. They highlighted IFNγ and cytolytic transcriptional signatures characteristic for this cutaneous leishmaniasis. Their findings included overexpression of genes encoding guanylate-binding proteins (GBPs): GBP1, GBP2, GBP3, GBP4, GBP5, and GBP6 and the pseudogene GBP1P1. All detected GBPs except GBP2 were positively correlated with cell type abundance scores for monocytes and macrophage/ monocyte-like cells using the microenvironment cell population counter. However, the complexity of GBPs involvement in anti-Leishmania responses deserves additional attention.

Frontiers in Immunology

Differences in frequencies of blood cell subpopulations were reported to influence the course of ... more Differences in frequencies of blood cell subpopulations were reported to influence the course of infections, atopic and autoimmune diseases, and cancer. We have discovered a unique mouse strain B10.O20 containing extremely high frequency of myeloid-derived cells (MDC) in spleen. B10.O20 carries 3.6% of genes of the strain O20 on the C57BL/10 genetic background. It contains much higher frequency of CD11b+Gr1+ cells in spleen than both its parents. B10.O20 carries O20-derived segments on chromosomes 1, 15, 17, and 18. Their linkage with frequencies of blood cell subpopulations in spleen was tested in F2 hybrids between B10.O20 and C57BL/10. We found 3 novel loci controlling MDC frequencies: Mydc1, 2, and 3 on chromosomes 1, 15, and 17, respectively, and a locus controlling relative spleen weight (Rsw1) that co-localizes with Mydc3 and also influences proportion of white and red pulp in spleen. Mydc1 controls numbers of CD11b+Gr1+ cells. Interaction of Mydc2 and Mydc3 regulates frequen...

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishman... more Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. There are three major clinical forms of leishmaniasis: cutaneous, mucocutaneous and visceral. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis caused by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe, effective and affordable drug and vaccine against L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infecti...

Trends in Endocrinology & Metabolism

Trends in Molecular Medicine

Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there ... more Age is a key risk factor associated with the severity of symptoms caused by SARS-Co-V2 and there is an urgent need to reduce COVID-19 morbidity and mortality in elderly individuals. We discuss evidence suggesting that trained immunity elicited by BCG vaccination may improve immune responses and can serve as a strategy to combat COVID-19 in this population.

... et al . Genetic immunization with gp63 DNA results in a helper T cell type 1 immune response ... more ... et al . Genetic immunization with gp63 DNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis; ashemi-Fesharaki R, Ale-Agha S, Habbibi GR, et al . Production of inactivated ...

European Heart Journal

On behalf of Yamanashi Kawasaki Disease Research Group Introduction: Kawasaki disease (KD) is an ... more On behalf of Yamanashi Kawasaki Disease Research Group Introduction: Kawasaki disease (KD) is an acute systemic vasculitis in children associated with increased inflammatory cytokines and immune-regulatory abnormalities. While the underlying cause of KD is unknown, the pathomechanism of KD involves a complex multicellular dysfunction of mononuclear cells such as CD14+CD16+ activated monocytes, T-helper type 17 (Th17) cells, and regulatory T (Treg) cells. In recent years, plasma exchange (PE) is effective treatment for KD patients refractory to IVIG at acute phase. The mechanism of PE was reported to directly remove the plasma levels of cytokines from the blood circulation. But the effect of PE on immune cells remains unknown. Purpose: To further investigate the mechanism of action of PE, we examined changes in the abundance of activated monocytes, Treg cells, and Th17 cells in KD patients following treatment with PE. Methods: This study included fourteen children who were treated with PE for IVIG-resistant KD at University Hospital. The mean age was 28 months (range: 4-90 months). Daily PE was performed for three consecutive days. We obtained the peripheral blood samples before and after PE and measured total leukocyte counts, fractional counts of leukocyte. We also measured the absolute counts of CD14+CD16+ monocytes, Treg cells and Th17 cells by flow cytometry, and serum levels of soluble IL-2 receptor, IL-6, and TNF-α by enzyme-linked immunosorbent assay. Results: Absolute white blood cell counts decreased significantly after PE. But the percentage of monocytes, lymphocytes and some subclasses of white blood cells, including CD3+, CD4+, CD8+ T cells, and CD19+ B cells were no significant difference between before and after PE. However, the percentage of CD14+CD16+ monocytes in white blood cells, and the percentage of CD14+CD16+ monocytes in total CD14+ monocytes all significantly decrease after PE (1.1±1.5 vs. 2.1±2.3%, p<0.05; 20.0±18.7 vs. 26.1±21.1%, p<0.05). The percentage of Th17 cells in white blood cells and Th17 cells in CD4+ T cells were not significantly changed after PE (0.4±0.4 vs. 0.3±0.4%; 2.7±2.7 vs. 2.0±2.0%). But the percentage of Treg cells in white blood cells and Treg cells in CD4+ T cells both significantly increased after PE (1.8±0.9 vs. 0.9±0.6%, p<0.01; 11.1±5.1 vs. 8.0±4.4%, p<0.05). Plasma concentrations of soluble IL-2 receptor, IL-6 decreased significantly after PE (1003±495 vs. 2118±631 U/mL, p<0.01; 8.8±8.5 vs. 139.8±159.3 pg/mL, p<0.01). However, the plasma concentration of TNF-α was not significantly changed after PE (5.4±3.6 vs. 7.5±6.1 pg/mL). Conclusion: In these results, the mechanisms of PE to heal the inflammation were related to decrease the ratio of activated CD14+CD16+ monocytes to white blood cells. Furthermore, PE increased the ratio of Treg to white blood cells and improve the Treg/Th17 cell imbalance in KD. P3795 2-arachidonoylglycerol activates pro-inflammatory pathways in murine macrophages and promotes atherogenesis in ApoE-/-mice