Plasmodium infection disrupts the T follicular helper cell response to heterologous immunization.
Plasmodium infection disrupts the T follicular helper cell response to heterologous immunization.
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DOI：
10.7554/elife.83330
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发表时间：
2023-01-30
期刊：
影响因子：
7.7
通讯作者：
Pepper M
中科院分区：
文献类型：
--
作者：
Fontana MF;Ollmann Saphire E;Pepper M
对疟疾的自然获得性免疫只有在多年和反复暴露后才会发展，这就提出了一个问题：疟疾的病原体疟原虫是否抑制树突状细胞（DC）激活最佳T细胞应答的能力。我们最近证明，B细胞，而不是树突状细胞，是小鼠疟疾中的CD4+ T细胞的主要活化剂。在本研究中，我们进一步研究了可能阻止DC引发疟原虫特异性T辅助细胞反应的因素。我们发现，与可溶性抗原相比，DC在摄取感染的红细胞（iRBC）方面的效率显著较低，而B细胞更容易结合iRBC。为了评估DC在疟疾期间是否保留呈现可溶性抗原的能力，我们测量了对未感染过疟原虫的小鼠或感染夏氏疟原虫的小鼠进行异源蛋白免疫的反应。抗原摄取、DC活化和免疫原特异性T细胞的扩增在感染小鼠中是完整的，表明DC保持功能。然而，免疫原特异性反应的极化显著改变，对免疫原特异性的生发中心T滤泡辅助细胞几乎完全丧失，伴随着抗原特异性B细胞和抗体的显著减少。我们的研究结果表明，树突状细胞仍然有能力激活T细胞在疟原虫感染，但T细胞极化和体液反应被严重破坏。这项研究提供了机制的洞察发展的疟原虫特异性和异源适应性反应的主机与疟疾。
Naturally acquired immunity to malaria develops only after many years and repeated exposures, raising the question of whether Plasmodium parasites, the etiological agents of malaria, suppress the ability of dendritic cells (DCs) to activate optimal T cell responses. We demonstrated recently that B cells, rather than DCs, are the principal activators of CD4+ T cells in murine malaria. In the present study, we further investigated factors that might prevent DCs from priming Plasmodium-specific T helper cell responses. We found that DCs were significantly less efficient at taking up infected red blood cells (iRBCs) compared to soluble antigen, whereas B cells more readily bound iRBCs. To assess whether DCs retained the capacity to present soluble antigen during malaria, we measured responses to a heterologous protein immunization administered to naïve mice or mice infected with P. chabaudi. Antigen uptake, DC activation, and expansion of immunogen-specific T cells were intact in infected mice, indicating DCs remained functional. However, polarization of the immunogen-specific response was dramatically altered, with a near-complete loss of germinal center T follicular helper cells specific for the immunogen, accompanied by significant reductions in antigen-specific B cells and antibody. Our results indicate that DCs remain competent to activate T cells during Plasmodium infection, but that T cell polarization and humoral responses are severely disrupted. This study provides mechanistic insight into the development of both Plasmodium-specific and heterologous adaptive responses in hosts with malaria.
影响因子：
7.3
作者：
Ueffing K;Abberger H;Westendorf AM;Matuschewski K;Buer J;Hansen W
通讯作者：
Hansen W
疟原虫菌株决定了疟疾生存至关重要的树突状细胞功能。
影响因子：
6.7
作者：
Wykes, Michelle N;Liu, Xue Q;Beattie, Lynette;Stanisic, Danielle I;Stacey, Katryn J;Smyth, Mark J;Thomas, Ranjeny;Good, Michael F
通讯作者：
Good, Michael F
影响因子：
6.7
作者：
Ng DH;Skehel JJ;Kassiotis G;Langhorne J
通讯作者：
Langhorne J