Preexisting helminth infection alters the metabolic state of tissue resident macrophages 2257375

Introduction Majority of the infections are coinfections. Previously, we showed that herpesvirus infection in mice with preexisting helminth infection increased infection and virus reactivation in tissue resident large peritoneal macrophages in a vitamin A dependent manner. The aim of this study is to determine the molecular mechanism underlying helminth-induced herpesvirus reactivation in large peritoneal macrophages. Methods Mice were first infected with Heligmosomoides polygyrus (HP), and then infected with murine gammaherpesvirus-68 (MHV68). Results With single cell RNA sequencing, we observed larger proportions of large peritoneal macrophages with HP-only infection and HP+MHV68 coinfection, which indicated expansion of these cells in these two conditions and not in uninfected or virus-only infection. Differential gene expression analysis of large peritoneal macrophages showed upregulation of metabolism pathways in coinfection and HP-only infection. Upon assessing metabolic flux in peritoneal macrophages, we observed higher mitochondrial respiration for coinfection and HP-only infection. Conclusion These observations suggest that intestinal helminth infection altered the metabolic state of resident macrophages in the peritoneal cavity, which may impact herpesvirus reactivation during coinfection. Further analysis of the mechanism is on-going.