Metabolic stress boosts humoral responses in vivo independently of inflammasome and inflammatory reaction

Adjuvant formulations boost humoral responses by acting through several, yet incompletely elucidated pathways. In this study, we show that oligomycin or 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) enhances Ab production when coinjected with T cell-dependent Ags. Oligomycin and AICAR lead to intracellular ATP reduction, suggesting that metabolic stress could be sensed by immune cells and leads to increased humoral responses. AICAR promotes IL-4 and IL-21 by naive Th cells but does not affect dendritic cell activation/maturation in vitro or in vivo. Accordingly, the adjuvant effect of AICAR or oligomycin does not require MyD88 or caspase-1 expression in vivo. Because AICAR is well tolerated in humans, this compound could represent a novel and safe adjuvant promoting humoral responses in vivo with a minimal reactogenicity.     

The Grey Mouse Lemur Uses Season-Dependent Fat or Protein Sparing Strategies to Face Chronic Food Restriction

During moderate calorie restriction (CR) the heterotherm Microcebus murinus is able to maintain a stable energy balance whatever the season, even if only wintering animals enter into torpor. To understand its energy saving strategies to respond to food shortages, we assessed protein and energy metabolisms associated with wintering torpor expression or summering torpor avoidance. We investigated body composition, whole body protein turnover, and daily energy expenditure (DEE), during a graded (40 and 80%) 35-day CR in short-days (winter; SD40 and SD80, respectively) and long-days (summer; LD40 and LD80, respectively) acclimated animals. LD40 animals showed no change in fat mass (FM) but a 12% fat free mass (FFM) reduction. Protein balance being positive after CR, the FFM loss was early and rapid. The 25% DEE reduction, in LD40 group was mainly explained by FFM changes. LD80 animals showed a steady body mass loss and were excluded from the CR trial at day 22, reaching a survival-threatened body mass. No data were available for this group. SD40 animals significantly decreased their FM level by 21%, but maintained FFM. Protein sparing was achieved through a 35 and 39% decrease in protein synthesis and catabolism (protein turnover), respectively, overall maintaining nitrogen balance. The 21% reduction in energy requirement was explained by the 30% nitrogen flux drop but also by torpor as DEE FFM-adjusted remained 13% lower compared to ad-libitum. SD80 animals were unable to maintain energy and nitrogen balances, losing both FM and FFM. Thus summering mouse lemurs equilibrate energy balance by a rapid loss of active metabolic mass without using torpor, whereas wintering animals spare protein and energy through increased torpor expression. Both strategies have direct fitness implication: 1) to maintain activities at a lower body size during the mating season and 2) to preserve an optimal wintering muscle mass and function.     

Chronic food shortage and seasonal modulations of daily torpor and locomotor activity in the grey mouse lemur (Microcebus murinus)

The extent to which seasonal plasticity in torpor displayed by one of the smallest Malagasy primates (Microcebus murinus) will help survival in the context of ongoing global change-induced chronic food shortage, is unknown. Body temperature (Tb) and locomotor activity were measured by telemetry in short- (SD, winter-acclimated) and long-days (LD, summer-acclimated) males (n = 24) during an experimental 35-day calorie restriction of 40 or 80%. Under SD exposure, regardless of calorie restriction intensity, mouse lemurs immediately increased torpor depth and duration by 4.6-fold, and showed greater phase-advanced entry into torpor (2.4-fold). Tb adjustments were efficient under 40% calorie restriction to maintain body mass, whereas they did not prevent a 0.71 +/- 0.11 g/day mass loss during 80% calorie restriction. The 40% food-deprived LD animals combined an early shallow deepening of torpor (1 degrees C) and a late 18% decrease in locomotor activity, resulting in a moderate 6% mass loss. After 15 days of 80% calorie restriction, LD animals exhibited a SD phenotype by increasing their torpor duration and phase-advancing the entry of torpor (16 min/day). Those adjustments had no impact on mass loss (0.93 +/- 0.07 g/day) as locomotor activity increased four-fold. Daily torpor allows M. murinus to face moderate food shortage whatever the photoperiod but poorly mitigates energy imbalance during severe food deprivation, especially under LD exposure. Although the behavioral thermoregulation role warrants further investigation in energy savings, M. murinus survival would be impaired during long-term food shortage in summer.     

Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces

Several H2-producing fermentative anaerobic bacteria including Clostridium, Klebsiella and Fusobacteria degraded octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) (36 microM) to formaldehyde (HCHO) and nitrous oxide (N2O) with rates ranging from 5 to 190 nmol h(-1)g [dry weight] of cells(-1). Among these strains, C. bifermentans strain HAW-1 grew and transformed HMX rapidly with the detection of the two key intermediates the mononitroso product and methylenedinitramine. Its cellular extract alone did not seem to degrade HMX appreciably, but degraded much faster in the presence of H2, NADH or NADPH. The disappearance of HMX was concurrent with the release of nitrite without the formation of the nitroso derivative(s). Results suggest that two types of enzymes were involved in HMX metabolism: one for denitration and the second for reduction to the nitroso derivative(s).