Deciphering Aedes aegypti-vertebrate host interactions at skin level by imaging mass spectrometry

Abstract

Aedes aegypti is a cosmopolitan mosquito species that transmits arboviruses that cause emerging and re-emerging diseases such as yellow fever, dengue, chikungunya and Zika. When attempting to feed on a vertebrate host, the Ae. aegypti mouthparts are inserted into the skin and saliva is deposited in this microenvironment, assisting in the location of blood vessels and counteracting molecules and resident cells responsible for the host's hemostasis, inflammatory and immune responses. Ae. aegypti saliva also triggers cutaneous allergic inflammation and is associated with the enhancement of viral infectivity. Frequent unanswered questions on the Ae. aegypti-vertebrate host interactions are related to the immunological environment created by mosquito saliva in the host skin, the effective amount of saliva that reaches the tissue during blood feeding and the dynamics of its distribution over time. In the present project, we propose to address these points by employing imaging mass spectrometry, a powerful technique capable of providing the spatial distribution of thousands of unlabeled molecules in tissue samples. A collaboration was established with Dr. Carlos Henrique Serezani and Dr. Julian F. Hillyer from Vanderbilt University in order to evaluate skin environment following Ae. aegypti bites having the support of the institutional Mass Spectrometry Research Center (MSRC). We expect to uncover the spatial and temporal dynamics of the mosquito saliva distribution in the skin, to provide in situ saliva quantification and to create a 3-dimensional map of inflammatory cells following mosquito bites. Such findings will contribute to refine our understanding on the mosquito-vertebrate host interactions in a molecular level. (AU)