Hematological Consequences of Environmental Change During Dewilding of Rhesus Macaques

The environment shapes immune system development and the ability to regulate 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 comprehensively assessed the immunological consequences in rhesus macaques as they transitioned from a natural outdoor provisioned environment to a quarantined laboratory facility in a process we term 'dewilding.' Dewilding led to a sharp drop in neutrophils and increased lymphocytes in the peripheral blood, a skewing toward a proinflammatory TH1 response, and increased T cell activation. 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 revealed increases in erythrocytes and their progenitors in the bone marrow, along with upregulation of genes involved in hemoglobin control and erythropoiesis. Notably, we also found that vaccination response was dampened when vaccination occurred earlier in the dewilding process. Together, our findings demonstrate 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. Overall design: Following the environmental transition of rhesus macaques from provisioned outdoor environment to indoor research facilities in a process called dewilding, nuclei were isolated from bone marrow samples and analyzed using snRNA-seq.