Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure

Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres. Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response. Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets

Adaptations architecturales du tissu osseux en réponse à l\u27exercice physique : intérêts et limites des méthodes non invasives utilisées chez l\u27homme

AimThe purpose of this paper is to give an overview of the imaging techniques that are currently used to study the effects of exercise on bone architecture.Current knowledgeIt is now widely accepted that the prevention of osteoporosis must be initiated in childhood, because the immature skeleton is more responsive to physical loading. Exercise recommendations for bone health promotion must consider the effects of loading not only on the more traditional measures of bone mineral content and macroarchitecture, but also on the microarchitecture and structural properties of the skeleton. The latter requires high precision 3D methods like quantitative computed tomography and magnetic resonance imaging.ProspectsImaging resolutions used most commonly in exercise studies of children have sufficient precision to assess bone density and gross geometry. However, they remain insufficient to clearly depict and quantify the trabecular bone microarchitecture in vivo in humans.<br /

Influence of puberty on muscle development at the forearm.

Despite its fundamental importance for physical development, the growth of the muscle system has received relatively little consideration. In this study, we analyzed the relationship between cross-sectional area (CSA) of forearm muscles and maximal isometric grip force with age and pubertal stage. The study population comprised 366 children, adolescents, and young adults from 6 to 23 yr of age (185 female) and 107 adults (88 female) aged 29 to 40 yr. By use of peripheral quantitative computed tomography, muscle CSA was determined at the site of the forearm, whose distance to the ulnar styloid process corresponded to 65% of forearm length. Both muscle CSA and grip force were higher in prepubertal boys than in girls. The gender differences decreased until pubertal stage 3 and reincreased thereafter. In girls at pubertal stage 5, muscle CSA no longer increased with age (P > 0.4), whereas there was still some age-related increase in grip force (P = 0.02). In boys at pubertal stage 5, both muscle CSA and grip force continued to increase significantly with age (P < 0.005 each). Specific grip force (grip force per muscle CSA) adjusted for forearm length increased by almost one-half between 6 and 20 yr of age, with no difference between the genders. In conclusion, forearm muscle growth takes a gender-specific course during puberty, indicating that it is influenced by hormonal changes. However, the increase in specific grip force is similar in both genders and thus appears to be independent of sex hormones

Functional fitness and bone mineral density in the elderly

Summary Bone quality has been associated with genetic factors and several environmental influences. This study suggests that although functional fitness should be consid ered in clinical assessments of bone health, body composi tion appears to have a higher relevance in the explanation of bone health/strength in older people. Purpose This study aims to describe the association be tween functional fitness (FF), other constitutive factors, and bone health/strength in a large community-dwelling sample of elderly active Portuguese. Methods This cross-sectional study included 401 males and 401 females aged 60–79 years old. Bone mineral density (BMD) of the total body, lumbar spine (LS), and hip region was determined by dual-energy X-ray absorptiometry (DXA). In addition, femur strength index (FSI) was deter mined. FF was assessed using the Senior Fitness Test. Demographic information and a health history were obtained by telephone interview through questionnaire. Results Aerobic endurance and body strength were pos itively related with hip BMD region in males (0.10<r< 0.16; p<0.01–0.05) and females (0.13<r<0.28; p< 0.01). No significant correlation was found between any FF test and LS BMD, except for upper-body strength in females. After controlling for other constitu tive predictors (sex, age, height, body mass (BM), total fat mass (TFM), and total lean tissue mass (TLTM)), FF had a minor contribution only in prediction of BMD at multisites and FSI. The total explained variance for all determinants was moderate (R²00.35 for femoral neck (FN) BMD, R²00.27 for LS BMD, R²00.49 total body BMD, and R²00.22 for FSI). Conclusions Sex, age, height, BM, TLTM, and TFM en tered as the most significant contributors for BMD and FSI. Although FF parameters are typically considered in clinical assessments of bone health/strength in older people, body composition appears to have a higher relevance in the explanation of BMD and strength.info:eu-repo/semantics/publishedVersio