UC San Diego

Homeostatic vigor is emerging as a pivotal determinant in an organism's capacity to weather health perturbations, particularly infectious diseases. The prevailing hypothesis suggests that hosts with greater vigor can mount a more robust defense against pathogens, thanks to their enhanced immune capabilities. To test this, we devised a model organism characterized by reduced vigor in the absence of an adaptive immune system. Our findings reveal that lower vigor correlates with a diminished survival rate during infection, not due to an impaired immune response, but because of a compromised metabolic and energetic equilibrium essential for overcoming pathogenic stress. This work complements the existing literature on cooperative defense systems that preserve health during infection without altering pathogen load.Simultaneously, we explored the less examined environmental determinant of sociality and its effects on infection response. Eusociality, as exemplified by species such as the naked mole rat (NMR), presents a unique opportunity to study the benefits and risks of social living. Our longitudinal observations of NMR colonies revealed that social turbulence, such as queen wars, precipitates fluctuations in the collective microbiome, impacting colony health. Moreover, the unprecedented discovery of a colony with two breeding queens coexisting peacefully prompts further study into this social anomaly. Extending our investigation to highly social but non-eusocial species, we found that social interaction during infection, contrary to causing social withdrawal, led to varied infection outcomes in mice. Surprisingly, cohabiting with Grin3a KO mice, which lack typical social behaviors, resulted in a worsened infection response in other mice, a phenomenon we linked to microbiome alterations through fecal microbiome transplants. Together, these studies underscore the intricate interplay between an organism's baseline state of vigor and its social environment, expanding our comprehension of how both intrinsic and external factors can profoundly influence the epidemiology and pathophysiology of infectious diseases.