Kamenyeva Olena, Boularan Cedric, Kabat Juraj, Cheung Gordon Y C, Cicala Claudia, Yeh Anthony J, Chan June L, Periasamy Saravanan, Otto Michael, Kehrl John H
B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Pathog. 2015 Apr 17;11(4):e1004827. doi: 10.1371/journal.ppat.1004827. eCollection 2015 Apr.
Neutrophils form the first line of host defense against bacterial pathogens. They are rapidly mobilized to sites of infection where they help marshal host defenses and remove bacteria by phagocytosis. While splenic neutrophils promote marginal zone B cell antibody production in response to administered T cell independent antigens, whether neutrophils shape humoral immunity in other lymphoid organs is controversial. Here we investigate the neutrophil influx following the local injection of Staphylococcus aureus adjacent to the inguinal lymph node and determine neutrophil impact on the lymph node humoral response. Using intravital microscopy we show that local immunization or infection recruits neutrophils from the blood to lymph nodes in waves. The second wave occurs temporally with neutrophils mobilized from the bone marrow. Within lymph nodes neutrophils infiltrate the medulla and interfollicular areas, but avoid crossing follicle borders. In vivo neutrophils form transient and long-lived interactions with B cells and plasma cells, and their depletion augments production of antigen-specific IgG and IgM in the lymph node. In vitro activated neutrophils establish synapse- and nanotube-like interactions with B cells and reduce B cell IgM production in a TGF-β1 dependent manner. Our data reveal that neutrophils mobilized from the bone marrow in response to a local bacterial challenge dampen the early humoral response in the lymph node.
中性粒细胞构成了宿主抵御细菌病原体的第一道防线。它们会迅速被动员到感染部位,在那里协助组织宿主防御并通过吞噬作用清除细菌。虽然脾脏中的中性粒细胞在对给予的非T细胞依赖性抗原作出反应时会促进边缘区B细胞抗体的产生,但中性粒细胞是否会影响其他淋巴器官中的体液免疫仍存在争议。在此,我们研究了在腹股沟淋巴结附近局部注射金黄色葡萄球菌后中性粒细胞的流入情况,并确定了中性粒细胞对淋巴结体液反应的影响。利用活体显微镜成像技术,我们发现局部免疫或感染会使中性粒细胞从血液中一波一波地募集到淋巴结。第二波募集在时间上与从骨髓动员的中性粒细胞同时发生。在淋巴结内,中性粒细胞浸润髓质和滤泡间区域,但不会越过滤泡边界。在体内,中性粒细胞与B细胞和浆细胞形成短暂和长期的相互作用,去除中性粒细胞会增加淋巴结中抗原特异性IgG和IgM的产生。在体外,活化的中性粒细胞与B细胞建立突触样和纳米管样的相互作用,并以TGF-β1依赖性方式减少B细胞IgM的产生。我们的数据表明,响应局部细菌攻击而从骨髓动员的中性粒细胞会抑制淋巴结中的早期体液反应。