Mast cells play a critical role in host defenses against Yersinia pestis (44.8)

Abstract

There is increasing evidence that mast cells play a role in host defenses, both via an IgE-FcεR mediated, allergy-like, response, as well as an IgG-FcγR mediated response. We provide evidence here that the inhibition of mast cell degranulation greatly enhances susceptibility of HLA-DQ8αβ transgenic (tg) mice to the plague. DQ8 tg mice are significantly more resistant to Yersinia pestis infection compared to out bred Swiss Webster mice, LD50 of >104 and 20 CFUs respectively. The magnitude of the resistance observed in DQ8 tg mice allowed us to examine the contribution of various immunological components during Y. pestis infection. To assess the role of mast cells, DQ8 tg mice were treated with cromolyn, a specific inhibitor of mast cell degranulation, prior to infection with Y. pestis. The enhanced resistance observed in DQ8 tg mice was completely eliminated with cromolyn treatment, suggesting an important role for mast cells in the host response of DQ8 tg mice to Y. pestis. We have previously reported that Y. pestis infected DQ8 tg mice develop a strong total IgG response, while infected Swiss Webster mice do not have any elevation in total IgG levels. The presence of elevated IgG levels may trigger the mast cell response in the DQ8 tg mice. These findings provide further evidence for a role of mast cells in host defenses and provide a model in which the molecular mechanisms of this interaction may be better understood.