Mast Cells Augment Adaptive Immunity by Orchestrating Dendritic Cell Trafficking through Infected Tissues

Abstract

Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that during E. coli infection, the primary humoral response in MC-deficient mice is significantly diminished, and was found to be less protective in a urinary tract infection (UTI) model compared to the response from MC-sufficient counterparts. MCs were found to recruit large numbers of dendritic cells (DCs) into the infected tissue site, which eventually migrated into draining lymph nodes (DLNs) over a prolonged time-course. This pattern of trafficking was facilitated by MC generated TNF, which increased the expression of E-selectin on local blood vessels. Antibody blockade of E-selectin inhibited DC recruitment into the site of infection and DLNs, and consequently impaired the primary humoral immune response. Thus, during infection, resident MCs contribute to the primary protective adaptive response through recruitment of DCs from the circulation into infected sites.

Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance

“…MCs can produce a wide range of cytokines after activation in response to varied stimuli, including pathogens or pathogen-associated products (1). TNF is a well-characterized product that MCs both prestore and produce de novo (26) and which is involved in varied innate as well as adaptive immune functions in the host, from promoting vascular changes to prompting swelling in DLNs (2,27). We observed that, within 1 h, TNF expression is significantly up-regulated by RBLs with stimulation by DENV2 and continues to increase remarkably over a 24-h period, as does another potent proinflammatory cytokine, IL-6 (Fig.…”

“…MCs not only resist DENV infection themselves but also appear to enhance the recruitment of NK and NKT cells to facilitate viral clearance. We previously reported TNF as mediating drastic changes to the host vasculature during bacterial infection, including promoting the expression of E-selectin on the vascular endothelium to facilitate leukocyte rolling in the vicinity of infection (2). Therefore, we expect that the MC-dependent cellular recruitment response that we observed during DENV infection is likely to involve chemotaxis of cells directed by MC-derived chemokines as well as the affects of other prestored and de novo-produced MC-derived factors, such as TNF.…”

“…These immediate, innate responses of MCs to pathogens can contribute to pathogen clearance (1). For example, bacteria or their products have been shown to initiate MC-driven processes, including promoting the trafficking of neutrophils into sites of infection, enhancing bacterial clearance, and promoting the movement of nonresident dendritic cells into infected skin (1)(2)(3). In contrast to their well-defined contributions to surveillance for bacteria and parasites, MC responses to viruses have hardly been examined (1).…”

Participation of mast cells in chronic otitis media

“…They can phagocytize bacteria and release pro-inflammatory mediators due to contact with bacteria and their products [3,4]. Mastocytes can also regulate the adaptive immunity to infection by modulation of dendritic cell and T-cell responses [3,7,8] and contribute to tissue remodeling in chronic inflammation [9].…”

Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis

“…[2][3][4][5] The mechanistic basis of MC-enhanced injury is by MC degranulation, which promotes injurious inflammation and enhances the capacity of dendritic cells (DCs) to drive autoimmunity. 6 Using these techniques, MCs have been demonstrated to be pathogenic in many diseases, including experimental autoimmune encephalomyelitis, 7 collagen induced arthritis, 8 type 1 diabetes mellitus (in non-obese diabetic mice), 9 bullous pemphigus 10 and systemic sclerosis. 11 The somewhat simplistic concept that MCs are only proinflammatory has been complicated by evidence demonstrating an essential role for MCs in the induction and maintenance of tolerance.…”