T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
复制标题
DOI：
10.1371/journal.ppat.1002660
复制
发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Andrew PW
中科院分区：
文献类型：
--
作者：
Neill DR;Fernandes VE;Wisby L;Haynes AR;Ferreira DM;Laher A;Strickland N;Gordon SB;Denny P;Kadioglu A;Andrew PW
肺炎链球菌是引起包括肺炎在内的一系列疾病的重要人类病原体。肺炎球菌感染期间在肺中诱导的免疫和促炎过程被很好地记录，但是关于免疫调节细胞和细胞因子在控制这种反应中所起的作用知之甚少。我们证明了肺炎球菌肺炎耐药BALB/c和敏感CBA/Ca小鼠品系之间免疫调节细胞因子转化生长因子（TGF）-β的显著差异。免疫组织化学和流式细胞术显示，在肺炎球菌肺炎期间，BALB/c肺中TGF-β蛋白水平较高，这与肺Foxp 3 +Helios+ T调节细胞的快速增加相关。这些细胞在肺炎球菌肺炎期间具有保护功能，因为用TGF-β抑制剂阻断它们的诱导会削弱BALB/c对感染的抵抗力，并有助于细菌从肺部传播。相反，在感染前，将调节性T细胞过继转移至CBA/Ca小鼠，可降低存活率并减少细菌从肺至血液的传播。重要的是，强烈的T调节细胞反应也与远交MF 1小鼠的抗病性相关，证实了免疫调节细胞在控制对肺炎球菌的保护性反应中的重要性。这项研究为肺肺炎球菌感染期间免疫调节的重要性提供了令人兴奋的新证据，并表明TGF-β信号转导是免疫治疗或药物设计的潜在靶点。 肺炎链球菌是一种主要的人类细菌病原体，可引起多种疾病，包括肺炎、脑膜炎、败血症和耳部感染。这种细菌每年造成约120万人死亡，主要是儿童、老年人和免疫系统薄弱的人等高危人群。肺炎球菌感染可引起多种免疫反应和疾病症状，目前尚不清楚为什么有些人比其他人对感染更具抵抗力。在这里，我们确定了一组细胞（称为T调节细胞）在天然抵抗肺炎球菌肺炎中的重要作用，这些细胞控制着对肺炎球菌感染的免疫反应。在小鼠中，强烈的调节性T细胞反应与对侵袭性肺炎球菌肺炎的抵抗力相关。疾病抵抗力可以通过给予高度易感小鼠T调节细胞来增强，或者通过阻断这些细胞在抗性小鼠中的活性来抑制。这些结果推进了我们对宿主免疫差异的理解，这些差异是对肺炎球菌肺炎的抵抗力的基础，并为未来我们可能通过调节易感个体的免疫系统来增强其抵抗力提供了希望。
Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design. Streptococcus pneumoniae is a major human bacterial pathogen that causes a wide range of diseases including pneumonia, meningitis, sepsis and ear infections. The bacterium is responsible for around 1.2 million deaths per year, mostly in high-risk groups such as children, the elderly and those with a weakened immune system. Infection with the pneumococcus can induce a wide-variety of immune responses and disease symptoms and it is not known why some people are more resistant to infection than others. Here, we identify an important role in natural resistance against pneumococcal pneumonia for a group of cells – known as T regulatory cells – that control the immune response to pneumococcal infection. In mice, strong T regulatory cell responses correlate with resistance to invasive pneumococcal pneumonia. Disease-resistance can be boosted by administering T regulatory cells to highly susceptible mice or inhibited by blocking the activity of these cells in resistant mice. These results advance our understanding of the host immunity differences that underpin resistance to pneumococcal pneumonia and offer hope that in the future we might boost resistance in susceptible individuals through modulation of their immune system.
登录
查看更多内容
影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
影响因子：
3.1
作者：
Kadioglu, A;Gingles, NA;Andrew, PW
通讯作者：
Andrew, PW
影响因子：
6.7
作者：
Buttery, J;Moxon, ER
通讯作者：
Moxon, ER
影响因子：
14.8
作者：
Fantini, Massimo C.;Dominitzki, Sabine;Becker, Christoph
通讯作者：
Becker, Christoph
DOI：
10.1164/ajrccm.160.supplement_1.4
发表时间：
1999-11-01
影响因子：
24.7
作者：
Haslett, C
通讯作者：
Haslett, C