Loke/Herbert

Project Title

Spatial transcriptomics of granulomas mediating resistance against helminth infection in different host genetic backgrounds

NIH Mentor

P’ng Loke

Penn Mentor

De’Broski Herbert

Project Details

How the genetic background of the host regulates the type-2 response expelling helminth parasites without excessive collateral tissue damage remains poorly understood. For example, BALB/C mice are resistant to Heligomosomoides polygyrus infection while C57BL/6 mice are susceptible, and while resistance to infection is known to require the formation of granulomas around the parasites, how and why this differs between strains is unclear. Recently, spatial transcriptomics provides a new tool to understand molecular mechanisms active in specific tissue locations, such as tissue granulomas. While our laboratories have a long-standing interest in characterizing macrophage responses to helminth infections, this new approach will provide a spatial context of the tissue microenvironment in which this reaction occurs, in a genetically susceptible and resistant host background. The results may provide insights into how noncoding genetic variation influences transcriptional regulatory networks in a spatially defined tissue microenvironment important for strain differential resistance against helminth parasites in mucosal tissues.