Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.

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Prenatal and Perinatal Environmental Influences Shaping the Neonatal Immune System: A Focus on Asthma and Allergy Origins

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083962 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3962

Author(s):

Azahara María García-Serna ◽

Elena Martín-Orozco ◽

Trinidad Hernández-Caselles ◽

Eva Morales

Keyword(s):

Immune System ◽

Immune Cell ◽

Mode Of Delivery ◽

Environmental Influences ◽

Pet Ownership ◽

System A ◽

Neonatal Immune System ◽

Chemical Factors ◽

Asthma And Allergy

It is suggested that programming of the immune system starts before birth and is shaped by environmental influences acting during critical windows of susceptibility for human development. Prenatal and perinatal exposure to physiological, biological, physical, or chemical factors can trigger permanent, irreversible changes to the developing immune system, which may be reflected in cord blood of neonates. The aim of this narrative review is to summarize the evidence on the role of the prenatal and perinatal environment, including season of birth, mode of delivery, exposure to common allergens, a farming environment, pet ownership, and exposure to tobacco smoking and pollutants, in shaping the immune cell populations and cytokines at birth in humans. We also discuss how reported disruptions in the immune system at birth might contribute to the development of asthma and related allergic manifestations later in life.

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From Intrauterine to Extrauterine Life—The Role of Endogenous and Exogenous Factors in the Regulation of the Intestinal Microbiota Community and Gut Maturation in Early Life

Frontiers in Nutrition ◽

10.3389/fnut.2021.696966 ◽

2021 ◽

Vol 8 ◽

Author(s):

Anna Socha-Banasiak ◽

Malwina Pawłowska ◽

Elżbieta Czkwianianc ◽

Kateryna Pierzynowska

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Human Life ◽

Antibiotic Use ◽

Lymphoid Cells ◽

Microbial Colonization ◽

Digestive Tube ◽

The Impact ◽

Gut Maturation

Differentiation of the digestive tube and formation of the gut unit as a whole, are regulated by environmental factors through epigenetic modifications which enhance cellular plasticity. The critical period of DNA imprinting lasts from conception until approximately the 1,000th day of human life. During pregnancy, besides agents that may directly promote epigenetic programming (e.g., folate, zinc, and choline supplementation), some factors (e.g., antibiotic use, dietary components) can affect the composition of the mother's microbiota, in turn affecting the fetal microbiome which interacts with the offspring's intestinal epithelial cells. According to available literature that confirms intrauterine microbial colonization, the impact of the microbiome and its metabolites on the genome seems to be key in fetal development, including functional gut maturation and the general health status of the offspring, as well as later on in life. Although the origin of the fetal microbiome is still not well-understood, the bacteria may originate from both the vagina, as the baby is born, as well as from the maternal oral cavity/gut, through the bloodstream. Moreover, the composition of the fetal gut microbiota varies depending on gestational age, which in turn possibly affects the regulation of the immune system at the barrier between mother and fetus, leading to differences in the ability of microorganisms to access and survive in the fetal environment. One of the most important local functions of the gut microbiota during the prenatal period is their exposure to foreign antigens which in turn contributes to immune system and tissue development, including fetal intestinal Innate Lymphoid Cells (ILCs). Additional factors that determine further infant microbiome development include whether the infant is born premature or at term, the method of delivery, maternal antibiotic use, and the composition of the mother's milk, among others. However, the latest findings highlight the fact that a more diverse infant gut microbiome at birth facilitates the proliferation of stem cells by microbial metabolites and accelerates infant development. This phenomenon confirms the unique role of microbiome. This review emphasizes the crucial perinatal and postnatal factors that may influence fetal and neonatal microbiota, and in turn gut maturation.

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The Role of Micronutrients in Support of the Immune Response against Viral Infections

Nutrients ◽

10.3390/nu12103198 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3198 ◽

Cited By ~ 1

Author(s):

Francesco Pecora ◽

Federica Persico ◽

Alberto Argentiero ◽

Cosimo Neglia ◽

Susanna Esposito

Keyword(s):

Fatty Acids ◽

Immune Response ◽

Immune System ◽

Viral Infections ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Optimal Function ◽

The Impact

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

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Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

International Journal of Molecular Sciences ◽

10.3390/ijms22179460 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9460

Author(s):

Helmut Segner ◽

Christyn Bailey ◽

Carolina Tafalla ◽

Jun Bo

Keyword(s):

Immune System ◽

Aryl Hydrocarbon Receptor ◽

Disease Susceptibility ◽

Immune Cell ◽

Physiological Role ◽

Immune Gene ◽

Immune Systems ◽

Aryl Hydrocarbon ◽

The Impact

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

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The Impact of Chronic Marijuana Exposure on Fetal Development in a Non-Human Primate Model

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2021.11.264 ◽

2022 ◽

Vol 226 (1) ◽

pp. S150

Author(s):

Rahul J. D'Mello ◽

Victoria H. Roberts ◽

Xiaojie Wang ◽

Juanito D. Terrobias ◽

Jamie O. Lo

Keyword(s):

Fetal Development ◽

Primate Model ◽

The Impact ◽

Human Primate

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Circulating Leukocytes and Oxidative Stress in Cardiovascular Diseases: A State of the Art

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2650429 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Speranza Rubattu ◽

Maurizio Forte ◽

Salvatore Raffa

Keyword(s):

Oxidative Stress ◽

Cardiovascular Diseases ◽

Stress Level ◽

Mononuclear Cells ◽

Pathological Condition ◽

Clinical Manifestations ◽

Therapeutic Interventions ◽

Oxidative Stress Level ◽

The Impact

Increased oxidative stress from both mitochondrial and cytosolic sources contributes to the development and the progression of cardiovascular diseases (CVDs), and it is a target of therapeutic interventions. The numerous efforts made over the last decades in order to develop tools able to monitor the oxidative stress level in patients affected by CVDs rely on the need to gain information on the disease state. However, this goal has not been satisfactorily accomplished until now. Among others, the isolation of circulating leukocytes to measure their oxidant level offers a valid, noninvasive challenge that has been tested in few pathological contexts, including hypertension, atherosclerosis and its clinical manifestations, and heart failure. Since leukocytes circulate in the blood stream, it is expected that they might reflect quite closely both systemic and cardiovascular oxidative stress and provide useful information on the pathological condition. The results of the studies discussed in the present review article are promising. They highlight the importance of measuring oxidative stress level in circulating mononuclear cells in different CVDs with a consistent correlation between degree of oxidative stress and severity of CVD and of its complications. Importantly, they also point to a double role of leukocytes, both as a marker of disease condition and as a direct contributor to disease progression. Finally, they show that the oxidative stress level of leukocytes reflects the impact of therapeutic interventions. It is likely that the isolation of leukocytes and the measurement of oxidative stress, once adequately developed, may represent an eligible tool for both research and clinical purposes to monitor the role of oxidative stress on the promotion and progression of CVDs, as well as the impact of therapies.

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The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective

Cancers ◽

10.3390/cancers12071849 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1849 ◽

Cited By ~ 4

Author(s):

Davide Brocco ◽

Rosalba Florio ◽

Laura De Lellis ◽

Serena Veschi ◽

Antonino Grassadonia ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adipose Tissue ◽

Molecular Mechanisms ◽

Normal Weight ◽

Therapeutic Options ◽

Therapeutic Interventions ◽

Fat Accumulation ◽

Adipose Organ ◽

The Impact

Pancreatic cancer (PC) is a lethal malignancy with rising incidence and limited therapeutic options. Obesity is a well-established risk factor for PC development. Moreover, it negatively affects outcome in PC patients. Excessive fat accumulation in obese, over- and normal-weight individuals induces metabolic and inflammatory changes of adipose tissue microenvironment leading to a dysfunctional adipose “organ”. This may drive the association between abnormal fat accumulation and pancreatic cancer. In this review, we describe several molecular mechanisms that underpin this association at both local and systemic levels. We focus on the role of adipose tissue-derived circulating factors including adipokines, hormones and pro-inflammatory cytokines, as well as on the impact of the local adipose tissue in promoting PC. A discussion on potential therapeutic interventions, interfering with pro-tumorigenic effects of dysfunctional adipose tissue in PC, is included. Considering the raise of global obesity, research efforts to uncover the molecular basis of the relationship between pancreatic cancer and adipose tissue dysfunction may provide novel insights for the prevention of this deadly disease. In addition, these efforts may uncover novel targets for personalized interventional strategies aimed at improving the currently unsatisfactory PC therapeutic options.

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Immunomodulation Part IV: Glutamine

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.25.6.439 ◽

2006 ◽

Vol 25 (6) ◽

pp. 439-443 ◽

Cited By ~ 3

Author(s):

Susan Givens Bell

Keyword(s):

Immune System ◽

Neonatal Morbidity ◽

Morbidity And Mortality ◽

Neonatal Immune System ◽

Indirect Stimulation

SEPSIS CONTINUES TO BE A significant cause of neonatal morbidity and mortality. Researchers have been exploring various modalities, including immunomodulation, as adjuncts to antibiotics to enhance the neonatal immune system. Generally, the role of the immunomodulators that have been studied is indirect stimulation or augmentation of the immune system.

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A Review of the Role Micronutrient Status in the Elderly Plays in Their Immune Response to Viral Respiratory Infections and the Potential Compromising Effects Medications Might Cause

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2020/v32i830468 ◽

2020 ◽

pp. 59-85

Author(s):

Michael P. Wakeman

Keyword(s):

Immune System ◽

Respiratory Infections ◽

The Elderly ◽

Micronutrient Status ◽

Viral Respiratory Infections ◽

The Impact ◽

Global Population ◽

Healthy Immune System ◽

Viral Respiratory

The elderly are a growing proportion of the global population. They are more susceptible to non-communicable diseases and respiratory viral diseases like influenza and covid19, which may lead to increased levels of morbidity and mortality than those of a younger generation. It is also reported that co-morbidities, especially diabetes, hypertension and coronary heart disease contribute significantly to the prognosis with these types of infections. That the immune system operates in a less efficient way as an individual ages, is now well understood and likely contributes significantly to this situation. The role of certain micronutrients in maintaining a healthy immune system is well recognised and demonstrated to play an important role both in preventing and controlling infection. However, for a number of reasons many elderly individuals have a less than optimal intake of many of the micronutrients that support the immune system. This review examines the contributory roles an aging immune system, suboptimal intake of micronutrients, comorbidities and the impact of the intake of medications typically used to treat them can play in the outcome of viral respiratory infections. It identifies the need for supplementation, especially in the elderly to support the immune system.

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Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques

10.1101/2021.01.25.428184 ◽

2021 ◽

Author(s):

C. M. Crooks ◽

A. M. Weiler ◽

S. L. Rybarczyk ◽

M. I. Bliss ◽

A. S. Jaeger ◽

...

Keyword(s):

Zika Virus ◽

Rhesus Macaques ◽

Maternal Plasma ◽

Adverse Outcomes ◽

Zikv Infection ◽

Primate Model ◽

Denv Serotypes ◽

The Impact ◽

Human Primate ◽

Maternal Fetal Interface

ABSTRACTConcerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

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