scholarly journals Chronic heat stress delays immune system development and alters serotonin signaling in pre-weaned dairy calves

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252474
Author(s):  
Marcela G. Marrero ◽  
Bethany Dado-Senn ◽  
Sena L. Field ◽  
Guan Yang ◽  
John P. Driver ◽  
...  
Keyword(s):  
Heat Stress ◽  
Immune System ◽  
Interleukin 6 ◽  
System Development ◽  
Late Gestation ◽  
Dairy Calves ◽  
Cell Counts ◽  
Immune System Development ◽  
Developmental Windows

Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A, -1F, -4 and -5 was greater, while heat shock protein 70 and immune-related genes (i.e., TBX21, TLR4, and TGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 after in-vitro lipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activated in-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens.

scholarly journals Mother-fetus immunogenetic dialogue as a factor of progeny immune system development

2019 ◽  
Vol 22 (8) ◽  
pp. 1009-1019
Author(s):  
L. A. Gerlinskaya ◽  
A. V. Varlachev ◽  
G. I. Krotov ◽  
G. V. Kontsevaya ◽  
M. P. Moshkin
Keyword(s):  
Molecular Weight ◽  
Immune System ◽  
Breast Milk ◽  
System Development ◽  
Large Body ◽  
Micro Rna ◽  
Surrogate Mothers ◽  
Immune System Development ◽  
Pass Through

Despite the advances in medicine, about 4 million children under the age of 6 months die annually around the world due to infection, which is 450 deaths per hour (UNISEF, 2009). The degree of development of the immune system of children born in time is determined by many factors, including the immunogenetic similarity or difference of mother and fetus organisms, which, in turn, is due to the genotypes of mating pairs, as well as the selection of surrogate mothers duringin vitrofertilization. From our review of the literature, it follows that immunogenetic interactions of mother and fetus organisms, which occur at all stages of pre- and postnatal development, have a signifcant effect on the resistance of offspring to infections and allergens. Before implantation, the mother’s immune responses are formed under the influence of semen fluid antigens, leukocytes and cytokines, as well as under the influence of the genes of the major histocompatibility complex, which are expressed in embryos at the stage of two cells. After implantation, transplacental transfer of immunoglobulins and immunocompetent cells becomes of immunomodulating importance. It is important to emphasize that, although substances with a high molecular weight usually do not pass through the placenta, this rule does not apply to immunoglobulin G (IgG), which, with a molecular weight of about 160 kDa, overcomes the transplacental barrier due to binding to the fetal Fc receptor. The level of IgG in newborns usually correlates with the level of maternal antibodies. During the period of natural feeding, the immune protection of newborns is provided by the mechanisms of innate immunity and the factors of humoral immunity of mothers. It has been shown that immunoglobulins from the milk of many animal species are transferred through the neonatal intestinal epithelium to the blood. Since breast milk contains large amounts of various immunoactive components, including proteins, cytokines, hormones, immunoglobulins, exosomes containing micro-RNA, and viable immune cells, the immunomodulating effects of breast milk persist even after elimination of maternal immunoglobulins from the blood of the offspring, up to maturation. Analysis of a large body of experimental data shows that the study of mechanisms of “motherfetus” and “mother-newborn” interactions are the basis of a knowledge base needed to fnd means of life-long directed modulation of the descendants’ immune status.

scholarly journals Immune system development varies according to age, location, and anemia in African children

2020 ◽  
Vol 12 (529) ◽  
pp. eaaw9522 ◽  
Author(s):  
Danika L. Hill ◽  
Edward J. Carr ◽  
Tobias Rutishauser ◽  
Gemma Moncunill ◽  
Joseph J. Campo ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
High Titer ◽  
Geographical Location ◽  
Cell Types ◽  
Iron Bioavailability ◽  
Immune System Development

Children from low- and middle-income countries, where there is a high incidence of infectious disease, have the greatest need for the protection afforded by vaccination, but vaccines often show reduced efficacy in these populations. An improved understanding of how age, infection, nutrition, and genetics influence immune ontogeny and function is key to informing vaccine design for this at-risk population. We sought to identify factors that shape immune development in children under 5 years of age from Tanzania and Mozambique by detailed immunophenotyping of longitudinal blood samples collected during the RTS,S malaria vaccine phase 3 trial. In these cohorts, the composition of the immune system is dynamically transformed during the first years of life, and this was further influenced by geographical location, with some immune cell types showing an altered rate of development in Tanzanian children compared to Dutch children enrolled in the Generation R population–based cohort study. High-titer antibody responses to the RTS,S/AS01E vaccine were associated with an activated immune profile at the time of vaccination, including an increased frequency of antibody-secreting plasmablasts and follicular helper T cells. Anemic children had lower frequencies of recent thymic emigrant T cells, isotype-switched memory B cells, and plasmablasts; modulating iron bioavailability in vitro could recapitulate the B cell defects observed in anemic children. Our findings demonstrate that the composition of the immune system in children varies according to age, geographical location, and anemia status.

Opinion on Immune Tolerance Therapeutic Development

2020 ◽  
Vol 48 (6) ◽  
pp. 712-717
Author(s):  
Zaher A. Radi ◽  
Thomas A. Wynn
Keyword(s):  
Immune System ◽  
Immune Tolerance ◽  
Tissue Injury ◽  
System Development ◽  
Pharmaceutical Drugs ◽  
Immune System Development ◽  
Therapeutic Development ◽  
Self Antigens

Immune tolerance is defined by an active state of immune system unresponsiveness to foreign and self-antigens. Loss of immune tolerance to self-antigens and the resulting overexpression of autoantibodies can lead to tissue injury and development of various autoimmune diseases. In drug development, the goal of newly emerging immune tolerance therapies is to treat autoimmune disorders by restoring the immunoregulatory capacity of the immune system. Development of immune tolerance targets is initiated with the establishment of pharmacological efficacy in relevant disease animal models, followed by their stepwise translation to humans. This review discusses the major challenges to developing tolerance inducing pharmaceutical drugs, including the selection of appropriate disease models to establish efficacy, adequate, and acceptable in vitro and in vivo safety assessments, relevant biomarkers of human safety and efficacy, and finally, some regulatory guidelines to successfully develop immune tolerance therapeutics. [Box: see text]

scholarly journals 216 Thermoregulatory and physiological responses of sows at different reproductive stages exposed to increasing ambient temperature

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 7-7
Author(s):  
Betty R McConn ◽  
Alan W Duttlinger ◽  
Kouassi R Kpodo ◽  
Jacob M Maskal ◽  
Brianna N Gaskill ◽  
...  
Keyword(s):  
Heat Stress ◽  
Ambient Temperature ◽  
Physiological Responses ◽  
Blood Gases ◽  
Respiratory Alkalosis ◽  
Stress Sensitivity ◽  
Late Gestation ◽  
Acid Base Balance ◽  
Study Objective ◽  
Cell Counts

Abstract Pregnant sows, especially during late-gestation, may be susceptible to heat stress due to increased metabolic heat production and body mass. Therefore, the study objective was to determine the thermoregulatory and physiological responses of sows exposed to increasing ambient temperature (TA) at 3 reproductive stages. In 3 repetitions, 27 multiparous sows (parity 3.22±0.89) were individually housed and had jugular catheters placed 5.0±1.0 d prior to the experiment. To differentiate between reproductive stages, sows were categorized as open (not pregnant, n=9), mid-gestation (59.7±9.6 days pregnant, n=9), or late-gestation (99.0±4.8 days pregnant, n=9). During the experiment, sows were exposed to 6 consecutive 1 h periods of increasing TA (period 1, 14.39±2.14°C; period 2, 16.20±1.39°C; period 3, 22.09±1.87°C; period 4, 26.34±1.39°C; period 5, 30.56±0.81°C; period 6, 35.07±0.96°C), with 1 h transition phases in between each period. Respiration rate (RR), heart rate (HR), skin temperature, and vaginal temperature (TV) were measured every 20 min and the mean was calculated for each period. At the end of each period, blood gases, leukocytes, and red blood cell counts were measured. Overall, RR and HR were greater (P≤0.04; 45.6% and 12.9%, respectively) in late-gestation versus mid-gestation sows. Compared to mid-gestation and open sows, TV tended to be greater (P=0.06) during period 4 (0.18°C and 0.29°C, respectively) and period 5 (0.14°C and 0.18°C, respectively) in late-gestation sows. Blood O2 increased (P< 0.01; 18.1%) for all sows with advancing period, regardless of reproductive stage. Late-gestation sows had reduced (P=0.02; 16.1%) blood CO2 compared to mid-gestation sows, regardless of period. In summary, late-gestation sows appear to be more sensitive to increasing TA as indicated by increased RR, HR, TV, and blood O2, and reduced blood CO2 when compared to mid-gestation or open sows. This change in O2 and CO2, due to increasing RR and heat stress sensitivity of late-gestation sows, may suggest an alteration to the acid-base balance, leading to respiratory alkalosis.

scholarly journals Osteopontin Levels in Human Milk Are Related to Maternal Nutrition and Infant Health and Growth

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2670
Author(s):  
Aysegül Aksan ◽  
Izzet Erdal ◽  
Siddika Songül Yalcin ◽  
Jürgen Stein ◽  
Gülhan Samur
Keyword(s):  
Immune System ◽  
Breast Milk ◽  
Infant Health ◽  
Maternal Nutrition ◽  
System Development ◽  
Maternal Factors ◽  
Immune System Development ◽  
The Mean ◽  
Pregnancy Weight

Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Methods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smoking, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels (p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = −0.284, p = < 0.001; r = −0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = −0.450, p = < 0.001; r = −0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0–3 months and breast milk OPN levels (r = −0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated.

scholarly journals 398 Towards new feeding approaches for optimizing nutritional status, immunity and host-microbiota interactions in neonatal and weaned piglets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 181-181
Author(s):  
Martin Lessard ◽  
Mylène Blais ◽  
Guylaine Talbot ◽  
J Jacques Matte ◽  
Ann Letellier ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Intestinal Microbiota ◽  
System Development ◽  
Feed Additives ◽  
Epithelial Cell Line ◽  
Host Immune System ◽  
Gut Health ◽  
Weaned Piglets ◽  
Immune System Development

Abstract Lactation, feeding conditions, microbial interventions and piglet growth in the first few weeks of life have important impact on the intestinal microbiota establishment and immune system development of piglets. Indeed, colostrum and milk contain various bioactive components such as immune factors, antimicrobial peptides and oligosaccharides that contribute to maintain intestinal homeostasis and regulate interactions between microbiota and host immune system. Recent results revealed that low birth weight piglet (LBWP) with poor weight gain during the first two weeks of life develop different intestinal microbiota and immune response profiles compared to high BWP (HBWP) littermates. Consequently, piglets within litters may have different resilience to infections after weaning and benefit from feed additives in a specific manner. A study has been performed to evaluate the potential of bovine colostrum extract (BC) as replacement to plasma proteins for improving gut health and resilience to Salmonella infection in piglets. Results revealed that in weaned piglets fed BC, intestinal microbiota was differently modulated and bacterial dysbiosis induced by Salmonella was restored faster. Moreover, expression of genes involved in innate immunity such as β-defensin-2 and glutathione peroxidase-2 was respectively down- and up-regulated in BC fed piglets. A combination of dietary supplementation with BC, cupper and vitamins A and D has also been tested in LBWP and HBWP, and there is clear evidence that BC in combination with other feed additives promote growth and gut health in both LBWP and HBWP. The porcine intestinal epithelial cell line IPEC-J2 was used to better understand the functional properties of BC. Results indicated that BC improves wound healing, enhances barrier function and modulates the expression of several genes involved in innate immune response. Finally, as microbial intervention, the potential of fecal transplantation to modulate intestinal microbiota and immune system development of piglets is under investigation and will be discussed.

scholarly journals VOLARE: Visual analysis of disease-associated microbiome-immune system interplay

2018 ◽  
Author(s):  
Janet C. Siebert ◽  
Charles Preston Neff ◽  
Jennifer M. Schneider ◽  
EmiLie H. Regner ◽  
Neha Ohri ◽  
...  
Keyword(s):  
Immune System ◽  
Web Application ◽  
Visual Analysis ◽  
System Development ◽  
Patient Specific ◽  
Domain Experts ◽  
Immune System Development ◽  
Interactive Environment ◽  
System Logs ◽  
Linear Regressions

AbstractBackgroundRelationships between specific microbes and proper immune system development, composition, and function have been reported in a number of studies. However, researchers have discovered only a fraction of the likely relationships. High-dimensional “omic” methodologies such as 16S ribosomal RNA (rRNA) sequencing and Time-of-flight mass cytometry (CyTOF) immunophenotyping generate data that support generation of hypotheses, with the potential to identify additional relationships at a level of granularity ripe for further experimentation. Pairwise linear regressions between microbial and host immune features is one approach for quantifying relationships between “omes”, and the differences in these relationships across study cohorts or arms. This approach yields a top table of candidate results. However, the top table alone lacks the detail that domain experts need to vet candidate results for follow-up experiments.ResultsTo support this vetting, we developed VOLARE (Visualization Of LineAr Regression Elements), a web application that integrates a searchable top table, small in-line graphs illustrating the fitted models, a network summarizing the top table, and on-demand detailed regression plots showing full sample-level detail. We applied VOLARE to three case studies—microbiome:cytokine data from fecal samples in HIV, microbiome:cytokine data in inflammatory bowel disease and spondyloarthritis, and microbiome:immune cell data from gut biopsies in HIV. We present both patient-specific phenomena and relationships that differ by disease state. We also analyzed interaction data from system logs to characterize usage scenarios. This log analysis revealed that, in using VOLARE, domain experts frequently generated detailed regression plots, suggesting that this detail aids the vetting of results.ConclusionsSystematically integrating microbe:immune cell readouts through pairwise linear regressions and presenting the top table in an interactive environment supports the vetting of results for scientific relevance. VOLARE allows domain experts to control the analysis of their results, screening dozens of candidate relationships with ease. This interactive environment transcends the limitations of a static top table.

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