Gambero Monica, Teixeira Daniela, Butin Liane, Ishimura Mayari Eika, Mariano Mario, Popi Ana Flavia, Longo-Maugéri Ieda Maria
Discipline of Immunology, Universidade Federal de São Paulo, Brazil.
Discipline of Immunology, Universidade Federal de São Paulo, Brazil.
Immunobiology. 2016 Sep;221(9):1001-11. doi: 10.1016/j.imbio.2016.03.003. Epub 2016 May 7.
B-1 lymphocytes are present in large numbers in the mouse peritoneal cavity, as are macrophages, and are responsible for natural IgM production. These lymphocytes migrate to inflammatory foci and are also involved in innate immunity. It was also demonstrated that B-1 cells are able to differentiated into phagocytes (B-1CDP), which is characterized by expression of F4/80 and increased phagocytic activity. B-1 cell responses to antigens and adjuvants are poorly characterized. It has been shown that Propionibacterium acnes suspensions induce immunomodulatory effects in both macrophages and B-2 lymphocytes. We recently demonstrated that this bacterium has the ability to increase B-1 cell populations both in vitro and in vivo. P. acnes induces B-1CDP differentiation, increases the expression of TLR2, TLR4 and TLR9 and augments the expression of CD80, CD86 and CD40 in B-1 and B-1CDP cells. Because P. acnes has been shown to modulate TLR expression, in this study, we investigated the role of TLR2 and TLR4 in B-1 cell population, including B-1CDP differentiation and phagocytic activity in vitro and in vivo. Interestingly, we have demonstrated that TLR2 signaling could be involved in the increase in the B-1 cell population induced by P. acnes. Furthermore, the early differentiation of B-1CDP is also dependent of TLR2. It was also observed that TLR signals also interfere in the phagocytic ability of B-1 cells and their phagocytes. According to these data, it is clear that P. acnes promotes an important adjuvant effect in B-1 cells by inducing them to differentiate into B-1CDP cells and modulates their phagocytic functions both in vivo and in vitro. Moreover, most of these effects are mediated primarily via TLR2. These data reinforce the findings that such bacterial suspensions have powerful adjuvant properties. The responses of B-1 cells to exogenous stimulation indicate that these cells are important to the innate immune response.
B-1淋巴细胞大量存在于小鼠腹腔中,巨噬细胞也是如此,它们负责天然IgM的产生。这些淋巴细胞迁移至炎症病灶,也参与先天免疫。研究还表明,B-1细胞能够分化为吞噬细胞(B-1CDP),其特征是表达F4/80并具有增强的吞噬活性。B-1细胞对抗原和佐剂的反应目前了解甚少。已表明痤疮丙酸杆菌悬液对巨噬细胞和B-2淋巴细胞均具有免疫调节作用。我们最近证明,这种细菌在体外和体内均具有增加B-1细胞群体的能力。痤疮丙酸杆菌可诱导B-1CDP分化,增加TLR2、TLR4和TLR9的表达,并增强B-1和B-1CDP细胞中CD80、CD86和CD40的表达。由于已证明痤疮丙酸杆菌可调节TLR表达,因此在本研究中,我们调查了TLR2和TLR4在B-1细胞群体中的作用,包括体外和体内B-1CDP的分化及吞噬活性。有趣的是,我们证明TLR2信号传导可能参与了痤疮丙酸杆菌诱导的B-1细胞群体增加。此外,B-1CDP的早期分化也依赖于TLR2。还观察到TLR信号也会干扰B-1细胞及其吞噬细胞的吞噬能力。根据这些数据,很明显痤疮丙酸杆菌通过诱导B-1细胞分化为B-1CDP细胞,在B-1细胞中发挥重要的佐剂作用,并在体内和体外调节其吞噬功能。此外,这些作用大多主要通过TLR2介导。这些数据强化了这样的发现,即此类细菌悬液具有强大的佐剂特性。B-1细胞对外源刺激的反应表明,这些细胞对先天免疫反应很重要。