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MSRC Proteomics Core Laboratory

Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions

AUTHORS

Cassat JEJames E , Moore JLJessica L , Wilson KJKevin J , Stark ZZach , Prentice BMBoone M , Van de Plas RRaf , Perry WJWilliam J , Zhang YYaofang , Virostko JJohn , Colvin DCDaniel C , Rose KLKristie L , Judd AMAudra M , Reyzer MLMichelle L , Spraggins JMJeffrey M , Grunenwald CMCaroline M , Gore JCJohn C , Caprioli RMRichard M , Skaar EPEric P . Science translational medicine. 2018 3 14; 10(432).

ABSTRACT

Diseases are characterized by distinct changes in tissue molecular distribution. Molecular analysis of intact tissues traditionally requires preexisting knowledge of, and reagents for, the targets of interest. Conversely, label-free discovery of disease-associated tissue analytes requires destructive processing for downstream identification platforms. Tissue-based analyses therefore sacrifice discovery to gain spatial distribution of known targets or sacrifice tissue architecture for discovery of unknown targets. To overcome these obstacles, we developed a multimodality imaging platform for discovery-based molecular histology. We apply this platform to a model of disseminated infection triggered by the pathogen , leading to the discovery of infection-associated alterations in the distribution and abundance of proteins and elements in tissue in mice. These data provide an unbiased, three-dimensional analysis of how disease affects the molecular architecture of complex tissues, enable culture-free diagnosis of infection through imaging-based detection of bacterial and host analytes, and reveal molecular heterogeneity at the host-pathogen interface.