Sytemic and Cellular Metabolic Phenotype of Infection and Immune Response to Listeria monocytogenes

Abstract

Abstract It is generally accepted that immune response and pathogen clearance are metabolically demanding. Additionally, shifts in cellular metabolism are known to occur during immune responses. However, we lack a grasp of how the numerous components of protective immunity contribute to the metabolic demand of illness. Previous studies using model antigens or purified PAMPs have been unable to represent the dynamics of live pathogen infection and immune response. Therefore, we sought to measure the systemic and cellular metabolism of infection and immune response to a well-characterized bacterial pathogen, Listeria monocytogenes. Mice infected with Listeria were monitored over the course of 12 days in multi-parameter metabolic cages. The metabolic phenotype data collected included body weight, activity, sleep, respiratory exchange rate, and energy expenditure. In a parallel study, mice infected with Listeria were utilized to measure bacterial burden, Listeria-specific T cell response, and cellular metabolism of the immune system. We found the early stages of infection (day 1–5), corresponding to the kinetics of the innate immune response, had the greatest metabolic impact on the organism as indicated by weight loss, reduced activity, increased sleep, and decreased energy expenditure. At later timepoints, corresponding to the timing of the adaptive response, there was little evidence of metabolic impact over uninfected controls. We also observed changes in myeloid cell metabolism over the course of the infection. Overall, our results indicate that the innate immune response is more metabolically demanding, compared to the adaptive immune response, linking “sickness behavior” to the timing of the innate immune response.