Bourges Dorothée, Meurens François, Berri Mustapha, Chevaleyre Claire, Zanello Galliano, Levast Benoît, Melo Sandrine, Gerdts Volker, Salmon Henri
Institut National de la Recherche Agronomique (INRA), UR1282, Infectiologie Animale et Santé Publique, F-37380, Nouzilly (Tours), France.
Mol Immunol. 2008 Jul;45(12):3354-62. doi: 10.1016/j.molimm.2008.04.017. Epub 2008 Jun 3.
In monogastric mammals, transfer of passive immunity via milk and colostrum plays an important role in protecting the neonate against mucosal infections. Here we analyzed the hypothesis that during gestation/lactation IgA+ plasmablasts leave the intestinal and respiratory surfaces towards the mammary gland (MG). We compared the recruitment of lymphocytes expressing homing receptors alpha4beta1 and alpha4beta7 to expression of their vascular counter-receptors, VCAM-1 and MAdCAM-1. Furthermore, the expression of the chemokines responsible for the recruitment of IgA+ plasmablasts was analyzed. Data confirmed that expressions of CCL28 and MAdCAM-1 in the MG increased during pregnancy and alpha4beta1+ and alpha4beta7+/IgA+ cell recruitment in lactation correlated with increase of CCL28 expression. Interestingly, VCAM-1 expression was found in small blood vessels of the lactating porcine MG, while in mice VCAM-1 was expressed in large blood vessels within the MG. Thus, our results indicate that the recruitment of IgA+ plasmablasts to MG is mediated by VCAM-1/alpha4beta1 and MAdCAM-1/alpha4beta7 in conjunction with CCL28/CCR10. They support the existence of a functional link between entero- and upper respiratory surfaces and MG, thereby, conferring protection against aero-digestive pathogens in the newborn.
在单胃哺乳动物中,通过乳汁和初乳传递被动免疫在保护新生儿免受黏膜感染方面发挥着重要作用。在此,我们分析了一个假设,即在妊娠/哺乳期,IgA+浆母细胞从肠道和呼吸道表面向乳腺迁移。我们比较了表达归巢受体α4β1和α4β7的淋巴细胞募集情况与其血管对应受体VCAM-1和MAdCAM-1的表达情况。此外,还分析了负责募集IgA+浆母细胞的趋化因子的表达。数据证实,乳腺中CCL28和MAdCAM-1的表达在妊娠期间增加,哺乳期α4β1+和α4β7+/IgA+细胞的募集与CCL28表达的增加相关。有趣的是,在泌乳猪的乳腺小血管中发现了VCAM-1的表达,而在小鼠中,VCAM-1在乳腺内的大血管中表达。因此,我们的结果表明,IgA+浆母细胞向乳腺的募集是由VCAM-1/α4β1和MAdCAM-1/α4β7与CCL28/CCR10共同介导的。它们支持肠道和上呼吸道表面与乳腺之间存在功能联系,从而为新生儿提供针对气源性消化病原体的保护。