Kenji Ishiwata - Academia.edu (original) (raw)

Papers by Kenji Ishiwata

Nature Communications, May 18, 2023

Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune resp... more Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully elucidated. Here, we assess the ontogenetic trajectory of basophils by single-cell RNA sequence analysis. Combined with flow cytometric and functional analyses, we identify c-Kit-CLEC12A hi pre-basophils located downstream of pre-basophil and mast cell progenitors (pre-BMPs) and upstream of CLEC12A lo mature basophils. The transcriptomic analysis predicts that the prebasophil population includes previously-defined basophil progenitor (BaP)like cells in terms of gene expression profile. Pre-basophils are highly proliferative and respond better to non-IgE stimuli but less to antigen plus IgE stimulation than do mature basophils. Although pre-basophils usually remain in the bone marrow, they emerge in helminth-infected tissues, probably through IL-3-mediated inhibition of their retention in the bone marrow. Thus, the present study identifies pre-basophils that bridge the gap between pre-BMPs and mature basophils during basophil ontogeny. Basophils are the least common granulocytes, comprising <1% of circulating leukocytes. They have several similarities with tissue-resident mast cells, including the expression of the high-affinity IgE receptor (FcεRI) on their cell surface and the prompt release of granule contents (degranulation) upon cross-linking of FcεRI. Therefore, basophils had mistakenly been regarded as blood-circulating surrogates of mast cells. However, the development of analytical tools for basophils, such as basophil-deficient mice 1,2 and basophil-reporter mice 3,4 , has enabled us to understand non-redundant functions of basophils in various immune responses 5-8 , including chronic allergic inflammation, autoimmune diseases, and protective immunity against parasitic infections. Basophils terminally differentiate within the bone marrow in contrast to mast cells, and several progenitor populations have been reported to differentiate into mature basophils 9. Unipotent basophil progenitors (BaPs) are identified in 2005 and defined as Lineage (Lin) − cKit − CD34 + FcεRIα + cells 10 or Lin − cKit − CD34 + CD200R3 + cells 11. As BaPs can be generated in vitro from granulocyte-macrophage progenitors (GMPs), they are considered as downstream of GMPs. Further studies identified bi-potential basophil and mast cell common progenitors in the bone marrow (pre-BMPs [Lin-Sca-1-cKit + CD34 + FcεRIα + FcγRII/III hi cells] and pro-BMPs [Lin − Sca-1 − cKit + CD34 + E-cadherin + FcγRII/ III hi cells]) 12,13. In addition, bi-potential basophil and mast cell common progenitor cells (BMCPs) have been identified also in the spleen 10 , even

Parasitology International, Dec 1, 2021

BACKGROUND Trichuris suis ova (TSO), with the potential to modulate the human immune system, have... more BACKGROUND Trichuris suis ova (TSO), with the potential to modulate the human immune system, have been tested for therapeutic application in autoimmune and allergic diseases such as inflammatory bowel disease (IBD). Previous clinical studies were limited to European and American participants, whereas Asian populations have not been well documented. In this study, a clinical trial was conducted to examine the safety and tolerability of TSO administration among a healthy Japanese population. METHODS The study was a randomized, double-blind, placebo-controlled trial held at Jikei University Hospital, Tokyo. Twelve volunteers were stratified into three groups receiving different doses of TSO (TSO 1000, 2500, and 7500) and another into the control group. These cases were limited to healthy Japanese men aged over 20 years old. Single doses of medicinal TSO or placebo were given to three participants of each group. All participants were followed up to 56 days after ingestion. During the follow-up period, clinical practitioners checked each participant at the clinic at 7, 14, 28, and 56 days post-ingestion (dpi). Clinical symptoms were evaluated using questionnaire-based self-reporting, which participants filled at every visit. Blood samples were drawn at 7, 14, 28, and 56 dpi. Fecal samples were collected at 28 and 56 dpi. RESULTS During the study period, twelve healthy Japanese male volunteers were enrolled. All participants completed the follow-up period. No severe adverse events were observed during the study period in all groups. Three participants in the TSO 1000, 2500, and 7500 groups had mild to moderate abdominal symptoms, diarrhea, bloating, and appetite loss during the observation period. One participant in the placebo group presented with mild diarrhea. Microscopic examination identified no parasite ova in any fecal samples. Blood sample examination indicated elevated eosinophil count in several cases, especially in the groups with the higher dose of TSO. No extra-abdominal symptoms were present in all cases. CONCLUSIONS Healthy Japanese people tolerated all doses of TSO without any severe adverse events. On the other hand, mild to moderate abdominal symptoms were observed in several participants. This study suggested that the medicinal use of TSO in Japan is relatively safe, and close follow-up is recommended for sustainable usage.

Journal of Immunology, May 1, 2019

Once mice experience the infection of helminth, the mice acquired resistance to the helminth. We ... more Once mice experience the infection of helminth, the mice acquired resistance to the helminth. We have studied about memory responses against Nippostrongylus brasiliensis (Nb) in mice. Nb penetrates into skin, passes through the lungs and finally reaches to the gut. It has been reported that IL-33 contributes to the immune responses against re-infection of helminth. However, the IL-33-dependent immunity to Nb has not been fully defined. In this study, we identified subsets of memory Th2 (mTh2) cells; CXCR5+ST2+CD44hiTh2 cells and ST2−CD44hiTh2 cells producing IL-4 and IL-13, and increasing accumulation of eosinophils in the lungs in helminth infection. CXCR5+ST2+mTh2 cells rather than ST2− mTh2 cells strongly expressed IL-5 and increased the expression of Major Basic Protein (MBP) in eosinophils in the lungs, which is important for reduction of maturation and fecundity of Nb in the intestine. Notably, we also found ST2+Treg cells but not ST2− Treg cells can suppress the ST2+mTh2 cell-mediated reduction of fecundity of Nb. Taken together, these findings indicate that we identified a mechanism against helminth elicited by a subpopulation of IL-5-producing Th2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs. This would be helpful to establish the drugs and/or vaccination against helminth,

Medical Entomology and Zoology, 2001

Parasitology International, 1998

Parasitology International, 1998

Parasitology International, 1998

The history of paragonimiasis in China has been more than 120 years, It is prevalent in 22 provin... more The history of paragonimiasis in China has been more than 120 years, It is prevalent in 22 provinces and municipalties of China. The number of cases are estimated around lOmillion. Eliology: Before 1949, only 3 species were known in China. Since 1957, 20 new species or subspecies have been repcrled.Among them.Sspecles are pathogenic for man. The Others am to be Mher invesl@led. Many new techniques and methods amused for taxonomic sludies.The P. westerrnanii have hvo subspecies (2n 6 3n Types) and the slender typas P. skrjabin and and P. uechuanensis in China may be Identical to the P. miyazakii in Japan, P is very interesting for sludles. First intermediate hosts: 25 species of fresh water snails belonging to thme families have been reocrtad. Secand intermediate hosts: 39 species of crustaceaus belcngirq to 6 families. The Iwo hcsl shrimps are Macrchrachium and Caridlna. Clinical studies: There are lwc clinical types of patqonlm&sls.one is westermani type, the second is szechuanens type. lmmuncdiagnc6is methods: Skin test for screening, CFT, dwble diffusion, electrcpheresis. IHA, IFA, ELISA and RlA have been used for detaclion of antkmdy; sandwich ELBA and monoclonal antibody ELlSA for detedion of dru~latory antiien IO evalue the effad of tmatment. Treatment: Praziquerdal is the first choice. 0_~22~EPIDEMIOLOGICAL FEATURES OF PARAGONIMIASIS OF YICHANG AREA, HUBEI, CENTRAL CHINA ZHa Cuang-xiang, Liu Yi-ren et al.

Journal of Wildlife Diseases, 1997

Gnathostoina doloresi parasitizes Hynobius. [In Japanese with English abstractl Igaku Kenkyim (Ac... more Gnathostoina doloresi parasitizes Hynobius. [In Japanese with English abstractl Igaku Kenkyim (Acta Medica) 22: 467-473.

Proceedings of the National Academy of Sciences, 2018

Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pa... more Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pathogenesis of diseases. While recent studies have characterized the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that induce immune responses against helminth infection remain unknown. We found that IL-5–producing CXCR6 + ST2 + CD44 + mTh2 cells play a crucial role in the IL-33–dependent inhibition of the fecundity of helminth, whereas other ST2 − mTh2 cells do not. Although both cell types induced the infiltration of granulocytes, especially eosinophils, into the lungs in response to helminth infection, the ST2 + mTh2 cell-induced eosinophils expressed higher levels of major basic protein (MBP), which is important for reducing the fecundity of Nippostrongylus brasiliensis (Nb), than ST2 − mTh2 cell-induced ones. Notably, we also found that ST2 + Treg cells but not ST2 − Treg cells suppressed CXCR6 + ST2 + mTh2 cell-mediated immune responses. Taken together, t...

Medical Entomology and Zoology, 2001

Medical Entomology and Zoology, 2001

Parasitology International, 1998

Glycobiology, 2019

Galactoseβ1-4Fucose (GalFuc) is a unique disaccharide found in invertebrates including nematodes.... more Galactoseβ1-4Fucose (GalFuc) is a unique disaccharide found in invertebrates including nematodes. A fungal galectin CGL2 suppresses nematode development by recognizing the galactoseβ1-4fucose epitope. The Caenorhabditis elegans galectin LEC-6 recognizes it as an endogenous ligand and the Glu 67 residue of LEC-6 is responsible for this interaction. We found that mammalian galectin-2 (Gal-2) also has a comparable glutamate residue, Glu 52. In the present study, we investigated the potential nematode-suppressing activity of Gal-2 using C. elegans as a model and focusing on Gal-2 binding to the GalFuc epitope. Gal-2 suppressed C. elegans development whereas its E52D mutant (Glu 52 substituted by Asp), galectin-1 and galectin-3 had little effect on C. elegans growth. Lectin-staining using fluorescently-labeled Gal-2 revealed that, like CGL2, it specifically binds to the C. elegans intestine. Natural C. elegans glycoconjugates were specifically bound by immobilized Gal-2. Western blotting with anti-GalFuc antibody showed that the bound glycoconjugates had the GalFuc epitope. Frontal affinity chromatography with pyridylamine-labeled C. elegans N-glycans disclosed that Gal-2 (but not its E52D mutant) recognizes the GalFuc epitope. Gal-2 also binds to the GalFuc-bearing glycoconjugates of Ascaris and the GalFuc epitope is present in the parasitic nematodes Nippostrongylus brasiliensis and Brugia pahangi. These results indicate that Gal-2 suppresses C. elegans development by binding to its GalFuc epitope. The findings also imply that Gal-2 may prevent infestations of various parasitic nematodes bearing the GalFuc epitope.

Phytochemistry Letters, 2018

Abstract On antiparasitic screening, we found that extracts of Peperomia japonica have nematicida... more Abstract On antiparasitic screening, we found that extracts of Peperomia japonica have nematicidal activity. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of one new polyketide (1), two new seco-lignans (2, 3), and two known polyketides (4, 5). The structures of these compounds were established by extensive one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry analyses. Compounds 1 and 4 show strong lethal activity toward Caenorhabditis elegans and Heligmosomoides polygyrus.

Immunology, 2018

Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the... more Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) and helper T lymphocytes (Th1 and Th2) was investigated using the spleen from rats fed zinc‐deficient or standard diet. In experiment I, 5‐week‐old male Sprague‐Dawley rats were fed a zinc‐deficient diet (without zinc additives) or a standard diet (containing 0·01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc‐deficient diets and were injected three times a week with either saline or interleukin‐4 (IL‐4) (zinc‐deficient/IL‐4 i.p.); a fourth group (zinc‐deficient/standard) was fed a zinc‐deficient diet for 6 weeks followed by a standard diet for 4 weeks. In experiment I; GATA‐binding protein 3 (GATA‐3) protein level, M2 macrophage, CD3+ CD8+ cells, and IL‐4/IL‐13‐positive cells significantly decreased in the spleens of the zinc‐deficient group. Additionally, IL‐1β and macrophage inflammatory protein‐1α (MIP‐1α) mRNA levels significantly increased in the splenic macrophages of the zinc‐deficient group. In experiment II; M2 macrophages, CD3+ CD8+ cells, IL‐4/IL‐13‐positive cells, and GATA‐3 protein levels significantly increased in the spleens of the zinc‐deficient/IL‐4 i.p. and zinc‐deficient/standard groups. Furthermore, IL‐1β and MIP‐1α mRNA levels decreased in the splenic macrophages of the zinc‐deficient/IL‐4 i.p. and zinc‐deficient/standard groups. Zinc deficiency‐induced aggravated inflammation is related to Th2 lymphocytes and followed by the association with loss of GATA‐3, IL‐4 and anti‐inflammatory M2 macrophages. Importantly, IL‐4 injection or zinc supplementation can reverse the effects of zinc deficiency on immune function.

Annals of Tropical Medicine & Parasitology, 2003

... to confirm whether or not the apparently causing human gnathostomiasis in the Americas. ... g... more ... to confirm whether or not the apparently causing human gnathostomiasis in the Americas. ... gnathostomiasis using antigens from Gnathostoma therefore be preferable to purifi ed antigens. ... If a purified antigen were to be used, Camacho, SPD, Ramos, MZ, Torrecillas, EP, ...

Communications Biology, 2021

The cryptic parasite Sparganum proliferum proliferates in humans and invades tissues and organs. ... more The cryptic parasite Sparganum proliferum proliferates in humans and invades tissues and organs. Only scattered cases have been reported, but S. proliferum infection is always fatal. However, S. proliferum’s phylogeny and life cycle remain enigmatic. To investigate the phylogenetic relationships between S. proliferum and other cestode species, and to examine the mechanisms underlying pathogenicity, we sequenced the entire genomes of S. proliferum and a closely related non–life-threatening tapeworm Spirometra erinaceieuropaei. Additionally, we performed larvae transcriptome analyses of S. proliferum plerocercoid to identify genes involved in asexual reproduction in the host. The genome sequences confirmed that the S. proliferum has experienced a clearly distinct evolutionary history from S. erinaceieuropaei. Moreover, we found that nonordinal extracellular matrix coordination allows asexual reproduction in the host, and loss of sexual maturity in S. proliferum are responsible for its...

Indian Journal of Tuberculosis

Nature Communications, May 18, 2023

Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune resp... more Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully elucidated. Here, we assess the ontogenetic trajectory of basophils by single-cell RNA sequence analysis. Combined with flow cytometric and functional analyses, we identify c-Kit-CLEC12A hi pre-basophils located downstream of pre-basophil and mast cell progenitors (pre-BMPs) and upstream of CLEC12A lo mature basophils. The transcriptomic analysis predicts that the prebasophil population includes previously-defined basophil progenitor (BaP)like cells in terms of gene expression profile. Pre-basophils are highly proliferative and respond better to non-IgE stimuli but less to antigen plus IgE stimulation than do mature basophils. Although pre-basophils usually remain in the bone marrow, they emerge in helminth-infected tissues, probably through IL-3-mediated inhibition of their retention in the bone marrow. Thus, the present study identifies pre-basophils that bridge the gap between pre-BMPs and mature basophils during basophil ontogeny. Basophils are the least common granulocytes, comprising <1% of circulating leukocytes. They have several similarities with tissue-resident mast cells, including the expression of the high-affinity IgE receptor (FcεRI) on their cell surface and the prompt release of granule contents (degranulation) upon cross-linking of FcεRI. Therefore, basophils had mistakenly been regarded as blood-circulating surrogates of mast cells. However, the development of analytical tools for basophils, such as basophil-deficient mice 1,2 and basophil-reporter mice 3,4 , has enabled us to understand non-redundant functions of basophils in various immune responses 5-8 , including chronic allergic inflammation, autoimmune diseases, and protective immunity against parasitic infections. Basophils terminally differentiate within the bone marrow in contrast to mast cells, and several progenitor populations have been reported to differentiate into mature basophils 9. Unipotent basophil progenitors (BaPs) are identified in 2005 and defined as Lineage (Lin) − cKit − CD34 + FcεRIα + cells 10 or Lin − cKit − CD34 + CD200R3 + cells 11. As BaPs can be generated in vitro from granulocyte-macrophage progenitors (GMPs), they are considered as downstream of GMPs. Further studies identified bi-potential basophil and mast cell common progenitors in the bone marrow (pre-BMPs [Lin-Sca-1-cKit + CD34 + FcεRIα + FcγRII/III hi cells] and pro-BMPs [Lin − Sca-1 − cKit + CD34 + E-cadherin + FcγRII/ III hi cells]) 12,13. In addition, bi-potential basophil and mast cell common progenitor cells (BMCPs) have been identified also in the spleen 10 , even

Parasitology International, Dec 1, 2021

BACKGROUND Trichuris suis ova (TSO), with the potential to modulate the human immune system, have... more BACKGROUND Trichuris suis ova (TSO), with the potential to modulate the human immune system, have been tested for therapeutic application in autoimmune and allergic diseases such as inflammatory bowel disease (IBD). Previous clinical studies were limited to European and American participants, whereas Asian populations have not been well documented. In this study, a clinical trial was conducted to examine the safety and tolerability of TSO administration among a healthy Japanese population. METHODS The study was a randomized, double-blind, placebo-controlled trial held at Jikei University Hospital, Tokyo. Twelve volunteers were stratified into three groups receiving different doses of TSO (TSO 1000, 2500, and 7500) and another into the control group. These cases were limited to healthy Japanese men aged over 20 years old. Single doses of medicinal TSO or placebo were given to three participants of each group. All participants were followed up to 56 days after ingestion. During the follow-up period, clinical practitioners checked each participant at the clinic at 7, 14, 28, and 56 days post-ingestion (dpi). Clinical symptoms were evaluated using questionnaire-based self-reporting, which participants filled at every visit. Blood samples were drawn at 7, 14, 28, and 56 dpi. Fecal samples were collected at 28 and 56 dpi. RESULTS During the study period, twelve healthy Japanese male volunteers were enrolled. All participants completed the follow-up period. No severe adverse events were observed during the study period in all groups. Three participants in the TSO 1000, 2500, and 7500 groups had mild to moderate abdominal symptoms, diarrhea, bloating, and appetite loss during the observation period. One participant in the placebo group presented with mild diarrhea. Microscopic examination identified no parasite ova in any fecal samples. Blood sample examination indicated elevated eosinophil count in several cases, especially in the groups with the higher dose of TSO. No extra-abdominal symptoms were present in all cases. CONCLUSIONS Healthy Japanese people tolerated all doses of TSO without any severe adverse events. On the other hand, mild to moderate abdominal symptoms were observed in several participants. This study suggested that the medicinal use of TSO in Japan is relatively safe, and close follow-up is recommended for sustainable usage.

Journal of Immunology, May 1, 2019

Once mice experience the infection of helminth, the mice acquired resistance to the helminth. We ... more Once mice experience the infection of helminth, the mice acquired resistance to the helminth. We have studied about memory responses against Nippostrongylus brasiliensis (Nb) in mice. Nb penetrates into skin, passes through the lungs and finally reaches to the gut. It has been reported that IL-33 contributes to the immune responses against re-infection of helminth. However, the IL-33-dependent immunity to Nb has not been fully defined. In this study, we identified subsets of memory Th2 (mTh2) cells; CXCR5+ST2+CD44hiTh2 cells and ST2−CD44hiTh2 cells producing IL-4 and IL-13, and increasing accumulation of eosinophils in the lungs in helminth infection. CXCR5+ST2+mTh2 cells rather than ST2− mTh2 cells strongly expressed IL-5 and increased the expression of Major Basic Protein (MBP) in eosinophils in the lungs, which is important for reduction of maturation and fecundity of Nb in the intestine. Notably, we also found ST2+Treg cells but not ST2− Treg cells can suppress the ST2+mTh2 cell-mediated reduction of fecundity of Nb. Taken together, these findings indicate that we identified a mechanism against helminth elicited by a subpopulation of IL-5-producing Th2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs. This would be helpful to establish the drugs and/or vaccination against helminth,

Medical Entomology and Zoology, 2001

Parasitology International, 1998

Parasitology International, 1998

Parasitology International, 1998

The history of paragonimiasis in China has been more than 120 years, It is prevalent in 22 provin... more The history of paragonimiasis in China has been more than 120 years, It is prevalent in 22 provinces and municipalties of China. The number of cases are estimated around lOmillion. Eliology: Before 1949, only 3 species were known in China. Since 1957, 20 new species or subspecies have been repcrled.Among them.Sspecles are pathogenic for man. The Others am to be Mher invesl@led. Many new techniques and methods amused for taxonomic sludies.The P. westerrnanii have hvo subspecies (2n 6 3n Types) and the slender typas P. skrjabin and and P. uechuanensis in China may be Identical to the P. miyazakii in Japan, P is very interesting for sludles. First intermediate hosts: 25 species of fresh water snails belonging to thme families have been reocrtad. Secand intermediate hosts: 39 species of crustaceaus belcngirq to 6 families. The Iwo hcsl shrimps are Macrchrachium and Caridlna. Clinical studies: There are lwc clinical types of patqonlm&sls.one is westermani type, the second is szechuanens type. lmmuncdiagnc6is methods: Skin test for screening, CFT, dwble diffusion, electrcpheresis. IHA, IFA, ELISA and RlA have been used for detaclion of antkmdy; sandwich ELBA and monoclonal antibody ELlSA for detedion of dru~latory antiien IO evalue the effad of tmatment. Treatment: Praziquerdal is the first choice. 0_~22~EPIDEMIOLOGICAL FEATURES OF PARAGONIMIASIS OF YICHANG AREA, HUBEI, CENTRAL CHINA ZHa Cuang-xiang, Liu Yi-ren et al.

Journal of Wildlife Diseases, 1997

Gnathostoina doloresi parasitizes Hynobius. [In Japanese with English abstractl Igaku Kenkyim (Ac... more Gnathostoina doloresi parasitizes Hynobius. [In Japanese with English abstractl Igaku Kenkyim (Acta Medica) 22: 467-473.

Proceedings of the National Academy of Sciences, 2018

Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pa... more Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pathogenesis of diseases. While recent studies have characterized the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that induce immune responses against helminth infection remain unknown. We found that IL-5–producing CXCR6 + ST2 + CD44 + mTh2 cells play a crucial role in the IL-33–dependent inhibition of the fecundity of helminth, whereas other ST2 − mTh2 cells do not. Although both cell types induced the infiltration of granulocytes, especially eosinophils, into the lungs in response to helminth infection, the ST2 + mTh2 cell-induced eosinophils expressed higher levels of major basic protein (MBP), which is important for reducing the fecundity of Nippostrongylus brasiliensis (Nb), than ST2 − mTh2 cell-induced ones. Notably, we also found that ST2 + Treg cells but not ST2 − Treg cells suppressed CXCR6 + ST2 + mTh2 cell-mediated immune responses. Taken together, t...

Medical Entomology and Zoology, 2001

Medical Entomology and Zoology, 2001

Parasitology International, 1998

Glycobiology, 2019

Galactoseβ1-4Fucose (GalFuc) is a unique disaccharide found in invertebrates including nematodes.... more Galactoseβ1-4Fucose (GalFuc) is a unique disaccharide found in invertebrates including nematodes. A fungal galectin CGL2 suppresses nematode development by recognizing the galactoseβ1-4fucose epitope. The Caenorhabditis elegans galectin LEC-6 recognizes it as an endogenous ligand and the Glu 67 residue of LEC-6 is responsible for this interaction. We found that mammalian galectin-2 (Gal-2) also has a comparable glutamate residue, Glu 52. In the present study, we investigated the potential nematode-suppressing activity of Gal-2 using C. elegans as a model and focusing on Gal-2 binding to the GalFuc epitope. Gal-2 suppressed C. elegans development whereas its E52D mutant (Glu 52 substituted by Asp), galectin-1 and galectin-3 had little effect on C. elegans growth. Lectin-staining using fluorescently-labeled Gal-2 revealed that, like CGL2, it specifically binds to the C. elegans intestine. Natural C. elegans glycoconjugates were specifically bound by immobilized Gal-2. Western blotting with anti-GalFuc antibody showed that the bound glycoconjugates had the GalFuc epitope. Frontal affinity chromatography with pyridylamine-labeled C. elegans N-glycans disclosed that Gal-2 (but not its E52D mutant) recognizes the GalFuc epitope. Gal-2 also binds to the GalFuc-bearing glycoconjugates of Ascaris and the GalFuc epitope is present in the parasitic nematodes Nippostrongylus brasiliensis and Brugia pahangi. These results indicate that Gal-2 suppresses C. elegans development by binding to its GalFuc epitope. The findings also imply that Gal-2 may prevent infestations of various parasitic nematodes bearing the GalFuc epitope.

Phytochemistry Letters, 2018

Abstract On antiparasitic screening, we found that extracts of Peperomia japonica have nematicida... more Abstract On antiparasitic screening, we found that extracts of Peperomia japonica have nematicidal activity. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of one new polyketide (1), two new seco-lignans (2, 3), and two known polyketides (4, 5). The structures of these compounds were established by extensive one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry analyses. Compounds 1 and 4 show strong lethal activity toward Caenorhabditis elegans and Heligmosomoides polygyrus.

Immunology, 2018

Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the... more Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) and helper T lymphocytes (Th1 and Th2) was investigated using the spleen from rats fed zinc‐deficient or standard diet. In experiment I, 5‐week‐old male Sprague‐Dawley rats were fed a zinc‐deficient diet (without zinc additives) or a standard diet (containing 0·01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc‐deficient diets and were injected three times a week with either saline or interleukin‐4 (IL‐4) (zinc‐deficient/IL‐4 i.p.); a fourth group (zinc‐deficient/standard) was fed a zinc‐deficient diet for 6 weeks followed by a standard diet for 4 weeks. In experiment I; GATA‐binding protein 3 (GATA‐3) protein level, M2 macrophage, CD3+ CD8+ cells, and IL‐4/IL‐13‐positive cells significantly decreased in the spleens of the zinc‐deficient group. Additionally, IL‐1β and macrophage inflammatory protein‐1α (MIP‐1α) mRNA levels significantly increased in the splenic macrophages of the zinc‐deficient group. In experiment II; M2 macrophages, CD3+ CD8+ cells, IL‐4/IL‐13‐positive cells, and GATA‐3 protein levels significantly increased in the spleens of the zinc‐deficient/IL‐4 i.p. and zinc‐deficient/standard groups. Furthermore, IL‐1β and MIP‐1α mRNA levels decreased in the splenic macrophages of the zinc‐deficient/IL‐4 i.p. and zinc‐deficient/standard groups. Zinc deficiency‐induced aggravated inflammation is related to Th2 lymphocytes and followed by the association with loss of GATA‐3, IL‐4 and anti‐inflammatory M2 macrophages. Importantly, IL‐4 injection or zinc supplementation can reverse the effects of zinc deficiency on immune function.

Annals of Tropical Medicine & Parasitology, 2003

... to confirm whether or not the apparently causing human gnathostomiasis in the Americas. ... g... more ... to confirm whether or not the apparently causing human gnathostomiasis in the Americas. ... gnathostomiasis using antigens from Gnathostoma therefore be preferable to purifi ed antigens. ... If a purified antigen were to be used, Camacho, SPD, Ramos, MZ, Torrecillas, EP, ...

Communications Biology, 2021

The cryptic parasite Sparganum proliferum proliferates in humans and invades tissues and organs. ... more The cryptic parasite Sparganum proliferum proliferates in humans and invades tissues and organs. Only scattered cases have been reported, but S. proliferum infection is always fatal. However, S. proliferum’s phylogeny and life cycle remain enigmatic. To investigate the phylogenetic relationships between S. proliferum and other cestode species, and to examine the mechanisms underlying pathogenicity, we sequenced the entire genomes of S. proliferum and a closely related non–life-threatening tapeworm Spirometra erinaceieuropaei. Additionally, we performed larvae transcriptome analyses of S. proliferum plerocercoid to identify genes involved in asexual reproduction in the host. The genome sequences confirmed that the S. proliferum has experienced a clearly distinct evolutionary history from S. erinaceieuropaei. Moreover, we found that nonordinal extracellular matrix coordination allows asexual reproduction in the host, and loss of sexual maturity in S. proliferum are responsible for its...

Indian Journal of Tuberculosis