Unimpaired Responses to Vaccination With Protein Antigen Plus Adjuvant in Mice With Kit-Independent Mast Cell Deficiency
Authors:
Open Access
- 28 August 2018
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 9, 1870
Abstract
Innate inflammatory responses are crucial for induction and regulation of T cell and antibody responses. Mast cell (MC)-deficient Kit mutant mice showed impaired adaptive immunity, suggesting that MCs provide essential adjuvant activities, and pharmacological MC activation was proposed as a new adjuvant principle. However, the Kit mutations result in complex alterations of the immune system in addition to MC deficiency. We revisited the role of MCs in vaccination responses using Mcpt5-Cre R26DTA/DTA and Cpa3Cre/+ mice that lack connective tissue MCs or all MCs, respectively, but feature an otherwise normal immune system. These animals showed no impairment of T and B cell responses to intradermal vaccination with protein antigen plus complete Freund’s adjuvant. Moreover, we demonstrate that the adjuvant effects of the MC secretagogue c48/80 in intradermal or mucosal immunization are independent of the presence of MCs. We hence find no evidence for a regulation by MCs of adaptive immune responses to protein antigens. The finding that immunological MC functions differ from those suggested by experiments in Kit mutants, emphasizes the importance of rigorous tests in Kit-independent MC-deficiency models.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (Ro2133/7, Ro2133/5-1, Ro2133/5-2, Ro2133/4, Du1172/2, DU1172/3, DU1172/4, SFB643-B15, SFB-TRR156-A07)
This publication has 75 references indexed in Scilit:
- Cre-Mediated Cell Ablation Contests Mast Cell Contribution in Models of Antibody- and T Cell-Mediated AutoimmunityImmunity, 2011
- Systems VaccinologyImmunity, 2010
- Mast cell-orchestrated immunity to pathogensNature Reviews Immunology, 2010
- Mast cell–derived particles deliver peripheral signals to remote lymph nodesJournal of Experimental Medicine, 2009
- Mast Cells Augment Adaptive Immunity by Orchestrating Dendritic Cell Trafficking through Infected TissuesCell Host & Microbe, 2009
- The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigenVaccine, 2009
- Mast cell deficiency in KitW-sh mice does not impair antibody-mediated arthritisJournal of Experimental Medicine, 2007
- Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII miceBlood, 2006
- Mast Cell-Deficient W-sash c-kit Mutant KitW-sh/W-sh Mice as a Model for Investigating Mast Cell Biology in VivoThe American Journal of Pathology, 2005
- Mast cell–derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infectionNature Immunology, 2003