Neutrophil Recruitment to Lymph Nodes Limits Local Humoral Response to Staphylococcus aureus

Abstract

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.

Neutrophils acquire the capacity for antigen presentation to memory CD4+ T cells in vitro and ex vivo

“…8,10,11 Antigen-positive neutrophils are found both in lymph nodes (LNs) and spleen, particularly under inflammatory conditions like infections and sterile inflammation. 10,[12][13][14][15][16] The migration of neutrophils to lymphoid organs both in humans and mice has been linked to upregulation of the chemokine receptor CCR7 and consequently is impaired in CCR7 2/2 mice. 17 Along with reaching lymphoid organs, it has been proposed that neutrophils contribute to adaptive immune responses by transporting and presenting antigen and regulating antigen-specific responses.…”

Enhancement of long-lasting immunoprotective effect against Androctonus australis hector envenomation using safe antigens: Comparative role of MF59 and Alum adjuvants

“…They indicated that neutrophil cells induce a reduction in key Ag-presenting molecules in dendritic cells through phagocytosis and trogocytosis process [27]. Another effect of neutrophil cells is to reduce directly the magnitude of humoral immune response toward bacteria antigens [28].…”

Recent advances in understanding neutrophils

“…Conversely, Kamenyeva et al . demonstrated that neutrophils recruited to the lymph following immunization or infection of the skin suppress antibody production by follicular B cells 92 . They showed by intravital microscopy that, upon entry into the lymph node from the circulation, neutrophils form long-term interactions with both B cells and plasma cells and block their ability to make antibodies through the secretion of TGF-β 92 .…”

“…Next-generation sequencing uses high-throughput platforms that can provide information regarding cell-specific transcriptome and gene regulation profiles. Combinations of these platforms, including single-cell sequencing approaches, have recently been employed to characterize myeloid progenitor and myeloid populations including neutrophils, defining signatures for different subsets 62, 102– 104 . Collectively, these techniques could provide additional context to functional differences between neutrophil subsets within a particular inflammatory setting, such as N1 and N2 neutrophils within the tumor microenvironment.…”