Brown-adipose-tissue macrophages control tissue innervation and homeostatic energy expenditure.

Tissue macrophages provide immunological defense and contribute to the establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator Mecp2 in macrophages. Mice that lacked the gene encoding Mecp2, which is associated with Rett syndrome, in macrophages did not show signs of neurodevelopmental disorder but displayed spontaneous obesity, which was linked to impaired function of brown adipose tissue (BAT). Specifically, mutagenesis of a BAT-resident Cx3Cr1+ macrophage subpopulation compromised homeostatic thermogenesis but not acute, cold-induced thermogenesis. Mechanistically, malfunction of BAT in pre-obese mice with mutant macrophages was associated with diminished sympathetic innervation and local titers of norepinephrine, which resulted in lower expression of thermogenic factors by adipocytes. Mutant macrophages overexpressed the signaling receptor and ligand PlexinA4, which might contribute to the phenotype by repulsion of sympathetic axons expressing the transmembrane semaphorin Sema6A. Collectively, we report a previously unappreciated homeostatic role for macrophages in the control of tissue innervation. Disruption of this circuit in BAT resulted in metabolic imbalance.

Costs of immune responses are related to host body size and lifespan.

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise, body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.

PHA-induced inflammation is not energetically costly in the subterranean rodent Ctenomys talarum (tuco-tucos).

Immune activity has been proposed to be associated with substantial costs, due to trade-offs with other functions or activities that share common resources and contribute to an animal's fitness. However, direct estimates of the cost of mounting an immune response are few and have been performed mainly in birds. Thus, further work is needed to clarify the relative costs of different components of the immune system and the role of environmental and life-history traits in modulating the costs of resistance. Within the components of immunity, inflammation is considered to be associated with a larger energetic expenditure. Here, we evaluated the energetic cost of the inflammatory response to phytohemagglutinin (PHA) in a wild population of a subterranean rodent, Ctenomys talarum, and the trade-offs between immune activity and reproduction. C. talarum develops an inflammatory response to PHA, but contrary to our predictions, this response was not associated with an increase in oxygen consumption regardless of reproductive status or sex. Our study shows that an immune challenge may not always result in a detectable energetic cost. We discuss the possibility that other currencies could be underlying the cost, such as micro-or macronutrients requirements, autoimmunity or oxidative stress.

Wild skylarks seasonally modulate energy budgets but maintain energetically costly inflammatory immune responses throughout the annual cycle.

A central hypothesis of ecological immunology is that immune defences are traded off against competing physiological and behavioural processes. During energetically demanding periods, birds are predicted to switch from expensive inflammatory responses to less costly immune responses. Acute phase responses (APRs) are a particularly costly form of immune defence, and, hence, seasonal modulations in APRs are expected. Yet, hypotheses about APR modulation remain untested in free-living organisms throughout a complete annual cycle. We studied seasonal modulations in the APRs and in the energy budgets of skylarks Alauda arvensis, a partial migrant bird from temperate zones that experiences substantial ecological changes during its annual cycle. We characterized throughout the annual cycle changes in their energy budgets by measuring basal metabolic rate (BMR) and body mass. We quantified APRs by measuring the effects of a lipopolysaccharide injection on metabolic rate, body mass, body temperature, and concentrations of glucose and ketone. Body mass and BMR were lowest during breeding, highest during winter and intermediate during spring migration, moult and autumn migration. Despite this variation in energy budgets, the magnitude of the APR, as measured by all variables, was similar in all annual cycle stages. Thus, while we find evidence that some annual cycle stages are relatively more energetically constrained, we find no support for the hypothesis that during these annual cycle stages birds compromise an immune defence that is itself energetically costly. We suggest that the ability to mount an APR may be so essential to survival in every annual cycle stage that skylarks do not trade off this costly form of defence with other annual cycle demands.

Mounting a specific immune response increases energy expenditure of the subterranean rodent Ctenomys talarum (tuco-tuco): implications for intraspecific and interspecific variation in immunological traits.

It was recently hypothesised that specific induced defences, which require substantial time and resources and are mostly beneficial against repeated infections, are more likely to be favoured in 'slow-living-pace' species. Therefore, understanding how different types of immune defences might vary with life history requires knowledge of the costs and benefits of defence components. Studies that have explored the energetic costs of immunity in vertebrates have done so with a focus primarily on birds and less so on mammals, particularly surface-dwelling rodents. In this study, we evaluated whether an experimental induction of the immune system with a non-pathogenic antigen elevates the energetic expenditure of a subterranean rodent: Ctenomys talarum (tuco-tucos). In both seasons studied, a significant increase in oxygen consumption was verified in immune-challenged tuco-tucos injected with sheep red blood cells (SRBC) compared with control animals. The increase in oxygen consumption 10 days after the exposure to SRBC was lower for female tuco-tucos monitored in the breeding season compared with females in the non-breeding season. Interestingly, antibody titres of female tuco-tucos did not decrease during the breeding season. Our results add new insight into the role of other factors such as basal metabolic rate or degree of parasite exposure besides 'pace of life' in modulating the interspecific immunological variation observed in natural populations of mammals.

Circulating white blood cell count and measures of adipose tissue inflammation predict higher 24-h energy expenditure.

OBJECTIVE: Energy expenditure (EE) and measures of inflammation increase with adiposity, and this obesity-induced chronic and subclinical inflammation was extensively reported to be a cause of insulin resistance. However, whether subclinical inflammation has a role in increasing EE, which may be at the cost of developing insulin resistance, is not clear. METHODS: We investigated the association between circulating white blood cell count (WBC) in a population of Native Americans (n=243) with measurement of EE in a respiratory chamber, and in a subset of the same population (n=34), with gene expression measures of inflammation in subcutaneous abdominal adipose tissue (SAAT). All subjects were healthy on oral glucose tolerance test. Statistically, nonnormally distributed variables were logarithmically transformed before analyses to approximate normal distributions. RESULTS: WBC was associated with 24-h EE adjusted for age, sex, fat-free mass, and fat mass (r=0.13, P=0.04). In SAAT, tumor necrosis factor-alpha (TNF-alpha), shown as log10-transformed TNF-alpha (r=0.36, P=0.05), and plasminogen activator inhibitor-1 (PAI-1), shown as log10-transformed PAI-1 (lPAI-1; r=0.41, P=0.02), expressions were also positively correlated with adjusted 24-h EE. lPAI-1 was also correlated with adjusted sleep EE (r=0.34, P=0.07). CONCLUSIONS: In conclusion, circulating markers of inflammation (WBC) and markers of inflammation within adipose tissue (TNF-alpha and PAI-1) are positively associated with EE, indicating a role of chronic subclinical inflammation in the regulation of metabolic rate.

Strength and cost of an induced immune response are associated with a heritable melanin-based colour trait in female tawny owls.

1. Melanin pigments provide the most widespread source of coloration in vertebrates, but the adaptive function of such traits remains poorly known. 2. In a wild population of tawny owls (Strix aluco), we investigated the relationships between plumage coloration, which varies continuously from dark to pale reddish, and the strength and cost of an induced immune response. 3. The degree of reddishness in tawny owl feather colour was positively correlated with the concentration of phaeomelanin and eumelanin pigments, and plumage coloration was highly heritable (h(2) = 0.93). No carotenoids were detected in the feathers. 4. In mothers, the degree of melanin-based coloration was associated with antibody production against a vaccine, with dark reddish females maintaining a stronger level of antibody for a longer period of time compared to pale reddish females, but at a cost in terms of greater loss of body mass. 5. A cross-fostering experiment showed that, independent of maternal coloration, foster chicks reared by vaccinated mothers were lighter than those reared by nonvaccinated mothers. Hence, even though dark reddish mothers suffered a stronger immune cost than pale reddish mothers, this asymmetric cost was not translated to offspring growth. 6. Our study suggests that different heritable melanin-based colorations are associated with alternative strategies to resist parasite attacks, with dark reddish individuals investing more resources towards the humoral immune response than lightly reddish conspecifics.

A high-mobility, low-cost phenotype defines human effector-memory CD8+ T cells.

T cells move randomly ("random-walk"), a characteristic thought to be integral to their function. Using migration assays and time-lapse microscopy, we found that CD8+ T cells lacking the lymph node homing receptors CCR7 and CD62L migrate more efficiently in transwell assays, and that these same cells are characterized by a high frequency of cells exhibiting random crawling activity under culture conditions mimicking the interstitial/extravascular milieu, but not when examined on endothelial cells. To assess the energy efficiency of cells crawling at a high frequency, we measured mRNA expression of genes key to mitochondrial energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1beta [PGC-1beta], estrogen-related receptor alpha [ERRalpha], cytochrome C, ATP synthase, and the uncoupling proteins [UCPs] UCP-2 and -3), quantified ATP contents, and performed calorimetric analyses. Together these assays indicated a high energy efficiency of the high crawling frequency CD8+ T-cell population, and identified differentially regulated heat production among nonlymphoid versus lymphoid homing CD8+ T cells.

Odour learning and immunity costs in mice.

There is accumulating evidence that learning is metabolically costly. One way in which this may manifest itself is in trade-offs between learning effort and immune function, with learning increasing susceptibility to infection. We tested this idea in the context of odour learning using outbred (BKW) male laboratory mice. Mice were exposed to three experimental treatments in which they were required to learn different numbers of urinary odours. While treatment affected the extent to which mice habituated to test odours during training, differences were not a simple function of the number of odours. The fact that there was also no significant effect of treatment on the degree of preference for novel over familiar odours in subsequent tests suggests mice retained learned odour profiles equally well regardless of the number of odours. That subsequent infection with Babesia microti increased with the number of odours mice had to learn is then consistent with an increased cost to learning effort when more odours were presented. Analysis within treatments, and relationships with the change in corticosterone concentration over the period of the experiment, suggested that it was a failure to learn, rather than maintaining learning performance, in more difficult learning tasks that led to greater infection. As in a previous study of maze learning in the strain, there was no direct relationship between infection and measures of peripheral antibody (total IgG) titre. The results are discussed in relation to studies in other learning contexts and reported relationships between glucocorticoid hormones and learning outcomes.

Estudio de gasto energético en especialistas militares de las tropas coheteriles antiaereas / Energetic budget among military specialists of Air Force Troops

Se realizó un estudio durante 6 meses, para conocer el gasto energético promedio de los especialistas de las Tropas Coheteriles Antiaéreas, (TCAA) por el método de cronometraje de actividades en 5 días tipo, representativos del trabajo de la especialidad en ese año. Se realizaron 30 cronometrajes a 12 hombres que constituyeron la muestra seleccionada aleatoriamente, dividida en tres grupos, según su peso. Estos especialistas se seleccionaron por su corpulencia y fortaleza física. La X del gasto energético (GE) en 24 horas, fue de 3 346 kcal o 14,0 MJ. El día tipo con mayor gasto fue el de guardia de seguridad y el menor el de preparación en materias generales. La jornada laboral (trabajo y preparación combativa fue de 10 horas y 10 min, con un máximo de tensión de trabajo en la mañana. El tiempo estaba compartido entre actividades militares, personales, sueño y tiempo libre. Sobre la base de estos resultados fueron elaborados recomendaciones de carácter nutricional para la especialidad