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P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria
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نویسنده
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salles é.m.d. ,menezes m.n.d. ,siqueira r. ,silva h.b.d. ,amaral e.p. ,castillo-méndez s.i. ,cunha i. ,cassado a.d.a. ,vieira f.s. ,olivieri d.n. ,tadokoro c.e. ,alvarez j.m. ,coutinho-silva r. ,d’império-lima m.r.
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منبع
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plos pathogens - 2017 - دوره : 13 - شماره : 8
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چکیده
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A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. however,it is still unclear whether recognition of damage signals influences the immune response to plasmodium infection. adenosine triphosphate (atp) accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. the p2x7 receptor senses extracellular atp and induces cd4 t cell activation and death. here we show that p2x7 receptor promotes t helper 1 (th1) cell differentiation to the detriment of follicular t helper (tfh) cells during blood-stage plasmodium chabaudi malaria. the p2x7 receptor was activated in cd4 t cells following the rupture of infected erythrocytes and these cells became highly responsive to atp during acute infection. moreover,mice lacking the p2x7 receptor had increased susceptibility to infection,which correlated with impaired th1 cell differentiation. accordingly,il-2 and ifnγ secretion,as well as t-bet expression,critically depended on p2x7 signaling in cd4 t cells. additionally,p2x7 receptor controlled the splenic tfh cell population in infected mice by promoting apoptotic-like cell death. finally,the p2x7 receptor was required to generate a balanced th1/tfh cell population with an improved ability to transfer parasite protection to cd4-deficient mice. this study provides a new insight into malaria immunology by showing the importance of p2x7 receptor in controlling the fine-tuning between th1 and tfh cell differentiation during p. chabaudi infection and thus in disease outcome. © 2017 salles et al.
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آدرس
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departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo,brazil,department of laboratory medicine and pathology,center of immunology,university of minnesota,minneapolis,mn, United States, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, escuela superior de enxeñaría informática,universidad de vigo,vigo, Spain, universidade vila velha,vila velha,es, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil, programa de imunobiologia,instituto de biofísica carlos chagas filho,universidade federal do rio de janeiro,rio de janeiro,brazil,instituto nacional de ciência e tecnologia para pesquisa translacional em saúde e meio ambiente da região amazônica,rio de janeiro, Brazil, departamento de imunologia,instituto de ciências biomédicas,universidade de são paulo,são paulo, Brazil
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Authors
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