Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization.
Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization.
复制标题
中性粒细胞对舌下免疫后负调节粘膜IgA反应的诱导。
作者：
能够提供针对细菌和病毒病原体的第一道防线的粘膜伊加的诱导仍然是经由粘膜途径给予的无针疫苗的主要目标。已知先天免疫细胞在粘膜疫苗诱导伊加应答中起核心作用，但骨髓细胞亚群对这些应答的相对贡献尚未确定。使用体内模型的舌下接种炭疽杆菌水肿毒素（EdTx）作为佐剂，我们研究了骨髓细胞亚群的粘膜分泌型伊加反应的作用。野生型小鼠的舌下免疫导致舌下组织和颈部淋巴结中中性粒细胞的短暂增加。这些小鼠后来产生了Ag特异性血清IgG反应，但没有血清或粘膜伊加。有趣的是，EdTx未能增加IKKβΔMye小鼠舌下组织中的中性粒细胞，这些小鼠产生伊加应答。在野生型小鼠免疫前中性粒细胞的部分消耗允许粘膜和血清伊加反应的发展。最后，将B细胞与来自野生型或IKKβΔMye小鼠的中性粒细胞共培养抑制伊加的产生，但不抑制IgM或IgG的产生。这些结果确定了一个新的角色，中性粒细胞作为伊加反应的负调节。
Induction of mucosal IgA capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. Using an in vivo model of sublingual vaccination with Bacillus anthracis edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type mice resulted in a transient increase of neutrophils in sublingual tissues and cervical lymph nodes. These mice later developed Ag-specific serum IgG responses, but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils in sublingual tissues of IKKβΔMye mice, and these mice developed IgA responses. Partial depletion of neutrophils before immunization of wild-type mice allowed the development of both mucosal and serum IgA responses. Finally, co-culture of B cells with neutrophils from either wild-type or IKKβΔMye mice suppressed production of IgA, but not IgM or IgG. These results identify a new role for neutrophils as negative regulators of IgA responses.
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影响因子：
--
作者：
Grespan, Renata;Fukada, Sandra Y.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.
影响因子：
6.7
作者：
Klezovich-Bénard M;Corre JP;Jusforgues-Saklani H;Fiole D;Burjek N;Tournier JN;Goossens PL
通讯作者：
Goossens PL
影响因子：
56.9
作者：
Jordan, MB;Mills, DM;Cambier, JC
通讯作者：
Cambier, JC
影响因子：
3.7
作者：
Jackson, Erin M.;Herbst-Kralovetz, Melissa M.
通讯作者：
Herbst-Kralovetz, Melissa M.
DOI：
10.1073/pnas.1002348107
发表时间：
2010-06-08
影响因子：
11.1
作者：
Datta, Sandip K.;Sabet, Mojgan;Raz, Eyal
通讯作者：
Raz, Eyal