Engulfment of mast cell secretory granules upon skin inflammation boosts dendritic cell migration and priming efficiency

Publication date: Available online 17 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Jan Dudeck, Julia Froebel, Johanna Kotrba, Christian H.K. Lehmann, Diana Dudziak, Stephan Speier, Sergei A. Nedospasov, Burkhart Schraven, Anne Dudeck

ABSTRACT

Background

Mast cells (MCs) are best known as key effector cells of allergic reactions but they also play an important role in host defense against pathogens. Despite increasing evidence for a critical impact of MCs on adaptive immunity, the underlying mechanisms are poorly understood.

Objective

Here, we monitored MC intercellular communication with dendritic cells (DCs), MC activation and degranulation and tracked the fate of exocytosed MC granules during skin inflammation.

Methods

Using a strategy to stain intracellular MC granules in vivo we tracked the MC granules fate following skin inflammation induced MC degranulation. Further, exogenous MC granules were applied to MC-deficient mice by intradermal injection. MC granule effects on DC functionality and adaptive immune responses in vivo were assessed by combining intravital multiphoton microscopy with flow cytometry and functional assays.

Results

We demonstrate that dermal DCs engulf the intact granules exocytosed by MCs upon skin inflammation. Subsequently, the engulfed MC granules are actively shuttled to skin-draining lymph nodes (LNs) and finally degraded inside DCs within the lymphoid tissue. Most importantly, MC-granule uptake promotes DC maturation and migration to skin-draining LNs, partially via MC-derived TNF, and boosts their T cell priming efficiency. Surprisingly, exogenous MC granules alone are sufficient to induce a prominent DC activation and T cell responses.

Conclusion

Our study highlights a unique feature of peripheral MCs to impact on lymphoid tissue borne adaptive immunity over distance by modifying DC functionality via the delivery of granule-stored mediators.

Graphical abstract

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