Imaging the Granzyme Mediated Host Immune Response to Viral and Bacterial Pathogens In Vivo Using Positron Emission Tomography

• DOI: 10.1021/acsinfecdis.4c00114
• Publication Date: 2024-05-31T13:57:28Z
• Authors: Apurva Pandey; Shalini Chopra; Simon J. Cleary; Marina López-Álvarez; Fiona M. Quimby; Aryn A.A. Alanizi; Sasank Sakhamuri; Ningjing Zhang; Mark R. Looney; Charles S. Craik; David M. Wilson; Michael J. Evans
• Keywords: Granzyme

Understanding how the host immune system engages complex pathogens is essential to developing therapeutic strategies overcome their virulence. While granzymes are well understood trigger apoptosis in infected cells or bacteria, less known about mobilizes individual granzyme species vivo combat diverse pathogens. Toward goal of studying function directly vivo, we previously developed a new class radiopharmaceuticals termed "restricted interaction peptides (RIPs)" that detect biochemically active endoproteases using positron emission tomography (PET). In this study, showed secreted B proteolysis response viral and bacterial could be imaged with [64Cu]Cu-GRIP B, RIP specifically targets B. Wild-type germline knockout mice were instilled intranasally A/PR/8/34 H1N1 influenza A strain generate pneumonia, production within lungs was measured PET/CT. Murine myositis models acute (E. coli, P. aeruginosa, K. pneumoniae, L. monocytogenes) infection also all cases, studied mPET/CT ex via tissue-harvesting, gamma counting, immunohistochemistry. uptake significantly higher wild-type received compared sham either treatment. mice, triceps muscle versus normal contralateral inoculated heat killed bacteria. above background not observed muscle. Interestingly, live monocytogenes did induce detectable on PET, despite prior vitro data, suggesting role for suppressing pathogenicity. summary, these data show elicited by human can PET. These results generated additional RIPs specific other proteases will allow deeper mechanistic study analysis biology.