Hematological Consequences of Environmental Change During Dewilding of Rhesus Macaques

The environment shapes immune system development and the regulation of inflammatory responses, which may affect the prevalence of immune mediated inflammatory diseases. However, the hematological consequences of a major environmental change, such as those experienced during migration, remain poorly understood. Here, we used cellular and molecular approaches to assess the immunological consequences in rhesus macaques as they transitioned from an outdoor provisioned environment to an indoor laboratory facility in a process we term ‘dewilding.’ Dewilding led to a sharp decrease in neutrophils and increased lymphocytes in the peripheral blood, a skewing toward a proinflammatory TH1 response, and increased T cell activation. Concurrently, we observed changes in the microbiome, with fungal abundance decreasing while bacterial abundance increased during dewilding. In the bone marrow, we observed increased granulopoiesis, reduced lymphocytes, and reduced hematopoietic stem cells and progenitors, with their shift toward less committed progenitor states. Single-cell nuclear RNA sequencing of the bone marrow revealed increased erythrocyte progenitors in the bone marrow during dewilding, with upregulation of genes involved in hemoglobin control and erythropoiesis. Notably, the vaccination response against measles varied based on vaccination period during the dewilding process. Together, our findings illustrate how dewilding alters immune homeostasis, with implications for understanding immune adaptation in migrants from rural to urban environments and for optimizing immunization strategies during environmental change.