Browsing by Author "Seki, T."

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Basophil depletion downregulates Schistosoma mansoni egg-induced granuloma formation
(Parasitology International, 2013-12) Anyan, W.K.; Seki, T.; Kumagai, T.; Obata-Ninomiya, K.; Furushima-Shimogawara, R.; Kwansa-Bentum, B.; Akao, N.; Bosompem, K.M.; Boakye, D.A.; Wilson, M.D.; Karasuyama, H.; Ohta, N.
Granuloma formation around parasite eggs during schistosomal infection is considered to be controlled by Th2 cytokines. However, it is still controversial which cell populations are responsible for the host Th2 cytokine-dependent granuloma formation. Basophils have recently attracted attention because of their ability to produce large amounts of IL-4. Therefore, we investigated whether basophils play an essential role in the induction of granuloma formation induced by Schistosoma mansoni eggs. Together with our previous observation that basophil numbers increased markedly in the spleen at 7. weeks postinfection, immunohistochemical staining using anti-mMCP8 monoclonal antibody (mAb) showed basophil infiltration in the granulomatous lesions formed around parasite eggs. To examine the roles of basophils more directly, we treated mice with anti-CD200R3 mAb to deplete basophils. Depletion of basophils resulted in a reduction of basophil number with concomitant downregulation of egg granuloma formation at 7. weeks postinfection. Moreover, we observed a significant reduction in the size of egg granulomas formed in basophil-depleted mice in the pulmonary granuloma model. Taken together, these findings indicated that basophils are essential for S. mansoni egg-induced granuloma formation, and this may serve as a novel therapeutic target in ameliorating the pathology of schistosomiasis. © 2013 Elsevier Ireland Ltd.
Interleukin-4 (IL-4) and IL-13 suppress excessive neutrophil infiltration and hepatocyte damage during acute murine schistosomiasis japonica
(Infection and Immunity, 2012) Seki, T.; Kumagai, T.; Kwansa-Bentum, B.; Furushima-Shimogawara, R.; Anyan, W.K.; Miyazawa, Y.; Iwakura, Y.; Ohta, N.
Due to the importance of neutrophils and proinflammatory cytokines in schistosomal liver damage, we analyzed the mechanisms underlying neutrophil and proinflammatory responses in murine schistosomiasis japonica. We found that granulomatous inflammation around parasite eggs in the liver was greater in Schistosoma japonicum-infected IL-4-/- IL-13-/- (double-knockout [DKO]) mice than in infected wild-type (WT) mice at 6 weeks, but not at 8 weeks, postinfection, suggesting the importance of Th2 responses in these typical hepatic lesions. Infected DKO mice also showed increased neutrophil infiltration accompanying more severe pathology, as shown by the enhanced necrosis of hepatocytes. This was not likely due to a Th1/Th2 imbalance, because there was no detectable increase in gamma interferon (IFN-γ) production in these DKO mice. mRNA expression of interleukin-17A (IL-17A), proinflammatory cytokines, and the neutrophil chemoattractant CXCL2 in liver was higher in infected DKO mice than in WT mice. However, in IL-4-/- IL-13-/- IL-17A-/- (triple-knockout [TKO]) mice, the absence of IL-17A was associated with only marginal differences in schistosomal liver damage, suggesting that IL-17A is only partially responsible for neutrophil-driven hepatic damage. Furthermore, the expression of mRNAs encoding proinflammatory cytokines was not under the control of IL-17A in TKO mice. These findings indicate that IL-4 and IL-13 suppress excessive neutrophil recruitment, proinflammatory cytokine production, and hepatic damage during the acute stage of S. japonicum infection, suggesting that neutrophils and proinflammatory cytokines are mainly responsible for hepatocyte damage during acute murine schistosomiasis japonica. However, neutrophil induction and the production of proinflammatory cytokines were not due solely to IL-17A.
Schistosome eggs have a direct role in the induction of basophils capable of a high level of IL-4 production: Comparative study of single- and bisexual infection of Schistosoma mansoni in vivo
(University of Ghana, 2010) Anyan, W.K.; Kumagai, T.; Rieko, F.; Shimogawara, F.K.; Seki, T.; Akao, N.; Obata, K.; Kwansa-Bentum, B.; Bosompem, K.M.; Boakye, D.A.; Wilson, M.; Karasuyama, H.; Ohta, N.
Immunobiological roles of schistosome eggs during murine experimental infection were investigated with special reference to the induction of basophilic leukocytes. After single- or bisexual infection with Schistosoma mansoni in BALB⁄c mice, splenomegaly and liver granulomas were observed only in bisexual infection in parallel with deposition of mature parasite eggs. Comparison of the kinetics of basophil response revealed a marked increase in number in the bone marrow of mice with bisexual infection at the 7th week post infection as opposed to a marginal increase in single- sex infections. In the spleen, bimodal response was observed in the basophil responses; a small but repeatable peak at the 4th week after infection, increasing again at the 8th week, which corresponded to the initiation and maturation of parasite eggs in the affected organs of infected mice. The same time course was observed for IL-4 production by the splenocytes from mice of bisexual infection. To obtain more concrete evidence of the role of eggs in the induction of basophils, we tested using the intravenous egg injection model. Injection of eggs induced basophilia, and it was accompanied by the up-regulation of IL-4 production in splenocytes from the 8th day. Basophils induced in this model showed a high level of IL-4 production confirmed by flow cytometry, while faint levels of IL-4 production were observed for CD4+ T cells at this time point. In addition, we demonstrate that egg deposition is the trigger of basophil induction and activation in the murine experimental model of S. mansoni infection, which might play an essential role in the initiation of Th1⁄2 conversion during the course of S. mansoni infection in vivo.
Schistosome eggs have a direct role in the induction of basophils capable of a high level of IL-4 production: Comparative study of single- and bisexual infection of Schistosoma mansoni in vivo
(International Journal of Tropical Insect Science, 2010) Anyan, W.K.; Kumagai, T.; Rieko, F.; Shimogawara, F.K.; Seki, T.; Akao, N.; Obata, K.; Kwansa-Bentum, B.; Bosompem, K.M.; Boakye, D.A.; Wilson, M.; Karasuyama, H.; Ohta, N.
Immunobiological roles of schistosome eggs during murine experimental infection were investigated with special reference to the induction of basophilic leukocytes. After single- or bisexual infection with Schistosoma mansoni in BALB⁄c mice, splenomegaly and liver granulomas were observed only in bisexual infection in parallel with deposition of mature parasite eggs. Comparison of the kinetics of basophil response revealed a marked increase in number in the bone marrow of mice with bisexual infection at the 7th week post infection as opposed to a marginal increase in single- sex infections. In the spleen, bimodal response was observed in the basophil responses; a small but repeatable peak at the 4th week after infection, increasing again at the 8th week, which corresponded to the initiation and maturation of parasite eggs in the affected organs of infected mice. The same time course was observed for IL-4 production by the splenocytes from mice of bisexual infection. To obtain more concrete evidence of the role of eggs in the induction of basophils, we tested using the intravenous egg injection model. Injection of eggs induced basophilia, and it was accompanied by the up-regulation of IL-4 production in splenocytes from the 8th day. Basophils induced in this model showed a high level of IL-4 production confirmed by flow cytometry, while faint levels of IL-4 production were observed for CD4+ T cells at this time point. In addition, we demonstrate that egg deposition is the trigger of basophil induction and activation in the murine experimental model of S. mansoni infection, which might play an essential role in the initiation of Th1⁄2 conversion during the course of S. mansoni infection in vivo.