Neutrophils Influence the Level of Antigen Presentation during the Immune Response to Protein Antigens in Adjuvants

Abstract

Neutrophils modulated antigen presentation following immunization with antigens in complete or incomplete Freund's adjuvant or alum. The neutrophils had an important negative role in the CD4 T cell and B cell responses to three protein antigens, hen-egg white lysozyme (HEL), ovalbumin (OVA) and listeriolysin O (LLO). In their absence (by depleting with antibodies for only the first twenty-four hours, or using genetically neutropenic mice), the cellular responses increased several fold. The CD8 response was not affected or slightly decreased. Competition for antigen between the presenting cells and the neutrophils, as well as an effect on the response to antigen-bearing dendritic cells (DC) was documented. Neutrophils entered the draining lymph nodes, rapidly and for a brief period of several hours, localizing mainly to the marginal sinus and superficial cortex. There they established brief contacts with DC and macrophages. Moreover, neutrophils imprinted on the quality of the subsequent DC-T cell interactions, despite no physical contacts with them: by intravital microscopy, the clustering of antigen-specific T cells and DC was improved in neutropenic mice. Thus, neutrophils are obligate cells that briefly enter sites of immunization and set the level of antigen presentation: a brief depletion may have a considerably positive impact on vaccination.

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

“…After migrating to the lymph nodes, neutrophils can compete with classic APCs (DCs, macrophages) to present antigens (47), and a direct interaction between antigen-pulsed neutrophils and CD8 T cells has also been proposed (9). In contrast, VACVinfected neutrophils cannot induce a CD8 T-cell proliferative response in BM in the absence of myeloid APCs (13).…”

Neutrophils Exhibit Differential Requirements for Homing Molecules in Their Lymphatic and Blood Trafficking into Draining Lymph Nodes

“…For many years, it was thought that emigration from tissues was only confined to lymphocytes and DCs, but not to granulocytes. Nevertheless, we and others have shown that neutrophils can migrate to LNs in response to different stimuli, such as inflammation (12)(13)(14) or infection (15)(16)(17)(18), where they shape the immune response by interacting with DCs and hence modulating Ag presentation (19). Indeed, we previously reported that, when OVA Ag is injected into hind footpads of previously OVA/CFA-immunized mice, the main OVA + cells in footpads and popliteal LNs (poLNs) are neutrophils (12).…”

Regulatory T Cells Prevent Inducible BALT Formation by Dampening Neutrophilic Inflammation

“…To our knowledge, this is the first study to describe a role for neutrophils in lymphoid neogenesis. This is somewhat surprising as neutrophils are one of the first inflammatory cells to be recruited to the site of sterile or infectious inflammation, can migrate from the inflammatory site to the draining lymph nodes, and are increasingly recognized as modulators of adaptive immunity (42)(43)(44). Indeed, neutrophils have been observed to infiltrate the iBALT area (12,45) as well as other TLOs (46,47), and are recruited in response to other TLR ligands or infectious pathogens shown to initiate iBALT formation in various animal species (4,48).…”

“…The mechanism by which Treg cells control neutrophils in the setting of iBALT development remains unclear; however, our data and that of Kocks et al (15) suggest that Treg cells mediate their effects in the MLN. Given that neutrophils are now appreciated to be among the first phagocytes to circulate from tissue sites to SLO (42,43), we speculate that Treg cells exert their anti-BALT-forming activity in this compartment. Potentially neutrophils may be able to counter-regulate this suppression through the production of cytokines such as IL-21.…”