The Role of Environmental Factors in Modulating Immune Responses in Early Life

The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved.

• Publication year

  2014

• Venue

  Frontiers in Immunology

• Publication date

  2014-09-12

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3389/fimmu.2014.00434PMID 25309535PMCID 4161944
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers.

  2014cited by this paper
• HIV‐exposed uninfected children: a growing population with a vulnerable immune system?

  2014cited by this paper
• The Effect of Maternal Helminth Infection on Maternal and Neonatal Immune Function and Immunity to Tuberculosis

  2014cited by this paper
• Immune response to Bordetella pertussis is associated with season and undernutrition in Senegalese children.

  2014cited by this paper
• In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants

  2014cited by this paper
• Arsenic Exposure Perturbs the Gut Microbiome and Its Metabolic Profile in Mice: An Integrated Metagenomics and Metabolomics Analysis

  2014cited by this paper
• Placental transfer and concentrations of cadmium, mercury, lead, and selenium in mothers, newborns, and young children

  2014cited by this paper
• Trained Immunity or Tolerance: Opposing Functional Programs Induced in Human Monocytes after Engagement of Various Pattern Recognition Receptors

  2014cited by this paper
• Pregnancy and infection.

  2014cited by this paper
• Altered Innate Immune Development in HIV-Exposed Uninfected Infants

  2014cited by this paper
• A Taxonomic Signature of Obesity in the Microbiome? Getting to the Guts of the Matter

  2014cited by this paper
• Pattern recognition receptor-mediated cytokine response in infants across 4 continents⋆☆

  2014cited by this paper
• Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials.

  2014cited by this paper
• Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

  2014cited by this paper
• Non-specific effect of Bacille Calmette-Guérin vaccine on the immune response to routine immunisations.

  2013cited by this paper
• Mode of Delivery and Inflammatory Disorders

  2013cited by this paper
• Colostrum-derived B and T cells as an extra-lymphoid compartment of effector cell populations in humans

  2013influential reference
• Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases.

  2013cited by this paper
• The human milk microbiota: origin and potential roles in health and disease.

  2013cited by this paper
• Beyond Stem Cells: Self-Renewal of Differentiated Macrophages

  2013influential reference
• Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

  2013cited by this paper
• Differential DNA Methylation in Umbilical Cord Blood of Infants Exposed to Low Levels of Arsenic in Utero

  2013cited by this paper
• Arsenic immunotoxicity: a review

  2013cited by this paper
• Human milk metagenome: a functional capacity analysis

  2013cited by this paper
• Nonspecific effects of vaccines and the reduction of mortality in children.

  2013cited by this paper
• Innate immune memory: implications for development of pediatric immunomodulatory agents and adjuvanted vaccines

  2013cited by this paper
• Early life response to infection

  2013cited by this paper
• Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease

  2013cited by this paper
• Pregnancy and Susceptibility to Infectious Diseases

  2013cited by this paper
• Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor

  2013cited by this paper
• Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine

  2013cited by this paper
• Nutrition in early life, immune-programming and allergies: the role of epigenetics.

  2013cited by this paper
• Developmental origins of non-communicable disease: Implications for research and public health

  2012cited by this paper
• Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly.

  2012cited by this paper
• Month of birth, vitamin D and risk of immune-mediated disease: a case control study

  2012cited by this paper
• Prenatal Arsenic Exposure and DNA Methylation in Maternal and Umbilical Cord Blood Leukocytes

  2012cited by this paper
• The lung tissue microbiome in chronic obstructive pulmonary disease.

  2012cited by this paper
• Serum vaccine antibody concentrations in children exposed to perfluorinated compounds.

  2012cited by this paper
• Maternal Geohelminth Infections Are Associated with an Increased Susceptibility to Geohelminth Infection in Children: A Case-Control Study

  2012cited by this paper
• Current Status of Developmental Immunotoxicity

  2012cited by this paper
• Pathogens and the placental fortress.

  2012cited by this paper
• Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

  2012cited by this paper
• The role of the placenta in fetal exposure to heavy metals

  2012cited by this paper
• Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections.

  2012cited by this paper
• Chronic maternal infections during pregnancy.

  2012cited by this paper
• HLA class I expression in the human placenta

  2012cited by this paper
• Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis.

  2012cited by this paper
• Influence of Socioeconomic Status Trajectories on Innate Immune Responsiveness in Children

  2012cited by this paper
• Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

  2012cited by this paper
• Interaction of pregnancy and autoimmune rheumatic disease.

  2012cited by this paper
• In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis.

  2012cited by this paper
• Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line

  2012cited by this paper
• HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life.

  2012cited by this paper
• Small Randomized Trial Among Low–birth-weight Children Receiving Bacillus Calmette-Guérin Vaccination at First Health Center Contact

  2012cited by this paper
• Trained immunity: a memory for innate host defense.

  2011cited by this paper
• Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants

  2011cited by this paper
• Unravelling the effects of the environment and host genotype on the gut microbiome

  2011cited by this paper
• Characterizing the Pregnancy Immune Phenotype: Results of the Viral Immunity and Pregnancy (VIP) Study

  2011cited by this paper
• In Utero Exposures, Infant Growth, and DNA Methylation of Repetitive Elements and Developmentally Related Genes in Human Placenta

  2011cited by this paper
• Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations.

  2011cited by this paper
• Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

  2011cited by this paper
• Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes.

  2011cited by this paper
• BCG Vaccination Induces Different Cytokine Profiles Following Infant BCG Vaccination in the UK and Malawi

  2011cited by this paper
• Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease

  2011cited by this paper
• Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

  2011cited by this paper
• In vitro evaluation of the immunotoxic potential of perfluorinated compounds (PFCs).

  2011cited by this paper
• Foxp3(+) regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens.

  2011cited by this paper
• Inflammatory mechanisms in obesity.

  2011cited by this paper
• Nutritionally mediated programming of the developing immune system.

  2011cited by this paper
• Cesarean versus vaginal delivery: long-term infant outcomes and the hygiene hypothesis.

  2011cited by this paper
• Effects of cessation of breastfeeding in HIV-1-exposed, uninfected children in Malawi.

  2011cited by this paper
• Cytokines in human milk.

  2010cited by this paper
• Molecular interactions in the placenta during malaria infection.

  2010cited by this paper
• Alcohol Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action and Maternal Treatment

  2010cited by this paper
• Role of innate host defenses in susceptibility to early-onset neonatal sepsis.

  2010cited by this paper
• Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

  2010influential reference
• Pre- and postnatal exposure to perfluorinated compounds (PFCs).

  2010cited by this paper
• Mercury exposure and children's health.

  2010cited by this paper
• Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues

  2010cited by this paper
• Decrease in the effectiveness of Bacille Calmette-Guérin vaccine against pulmonary tuberculosis: a consequence of increased immune suppression by microbial antioxidants, not overattenuation.

  2010cited by this paper
• Role of diet in the development of immune tolerance in the context of allergic disease

  2010cited by this paper
• Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns

  2010cited by this paper
• Epigenetic modifications and human disease

  2010cited by this paper
• Evidence for in utero sensitization to Ascaris lumbricoides in newborns of mothers with ascariasis.

  2009cited by this paper
• Developmental Origins of Health and Disease: Brief History of the Approach and Current Focus on Epigenetic Mechanisms

  2009influential reference
• Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses

  2009cited by this paper
• Effects of arsenic on maternal and fetal health.

  2009cited by this paper
• Do Antenatal Parasite Infections Devalue Childhood Vaccination?

  2009cited by this paper
• Developmental immunotoxicology: focus on health risks.

  2009cited by this paper
• Prenatal and childhood Mediterranean diet and the development of asthma and allergies in children

  2009cited by this paper
• Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia.

  2009cited by this paper
• Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults1

  2009influential reference
• The gut microbiota shapes intestinal immune responses during health and disease

  2009cited by this paper
• Induction of antigen-specific immunity in human neonates and infants.

  2008influential reference
• Birth season and environmental influences on blood leucocyte and lymphocyte subpopulations in rural Gambian infants

  2008cited by this paper
• Survival of Infants Born to HIV-Positive Mothers, by Feeding Modality, in Rakai, Uganda

  2008cited by this paper
• Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin

  2008cited by this paper
• HIV, infant feeding and more perils for poor people: new WHO guidelines encourage review of formula milk policies.

  2008cited by this paper
• Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study.

  2008cited by this paper
• Immune cell counts and risks of respiratory infections among infants exposed pre- and postnatally to organochlorine compounds: a prospective study

  2008cited by this paper

• Innate Immune Activation Beyond Pathogens: Crosstalk between Cellular Repair Pathways and DAMPs in Homeostatic Inflammation.

  2026cites this paper
• Integrating Exposures and Multi-Omics in the Boston Birth Cohort to Elucidate Immune Development across the Life Course: Rationale and Study Design.

  2025cites this paper
• Evaluation of Selected Trace Metals' Imbalances in the Whole Blood of Juvenile Idiopathic Arthritis Patients in Comparison with Healthy Subjects.

  2025cites this paper
• Ethnicity and sub-Saharan African representation in the emergency development of covid-19 vaccines

  2025cites this paper
• Kawasaki Disease in Adolescents: Current Knowledge, Clinical Challenges, and Long-Term Care

  2025cites this paper
• Interaction between gut microbiota and immunity in health and intestinal disease

  2025cites this paper
• Physical Activity for Human and Planetary Health: Incorporating Green Exercise in the Management of Rheumatic Disease.

  2025cites this paper
• Associations between exposure to metals, chlorinated pesticides, and PCBs and differential leukocyte profiles in Flemish adolescents.

  2025cites this paper
• Proximity effects and disease-related differences in DNA methylation among asthma patients near the Sohar Industrial Port, Oman.

  2025cites this paper
• Early Life PBDE Flame Retardant Exposures Cause Neurobehavioral Alterations in Fish That Persist into Adulthood and Vary by Sex and Route of Exposure

  2025cites this paper
• Heritable and environmental influences on innate immunity across three populations of threespine stickleback (Gasterosteus aculeatus)

  2025cites this paper
• Atopy-related immune profiles are subject to genetic influence as evaluated using school-aged twin pairs

  2025cites this paper
• Is environmental enrichment effective in modulating autophagy markers in the brain exposed to adverse conditions? A systematic review

  2025cites this paper
• From Womb to Mind: Prenatal Epigenetic Influences on Mental Health Disorders

  2025cites this paper
• Peculiarities of the immune status in children with nervous system pathology combined with excessive contamination of biological media with aluminum

  2025cites this paper
• Early-life PBDE flame retardant exposures cause neurobehavioral alterations in fish that persist into adulthood and vary by sex and route of exposure

  2025cites this paper
• Sex-specific disease resistance and gut microbiota dynamics in juvenile common carp (Cyprinus carpio) following viral infection

  2025cites this paper
• Immunomodulatory potential of phosphorus: insights from experimental mice models under normal and immunosuppressive condition

  2025cites this paper
• Immunological Avalanches in Renal Immune Diseases

  2025cites this paper
• Metabolomic studies of respiratory infections in early life: A narrative review

  2025cites this paper
• Modulation of immune gene expression profile in Labeo catla with chronic toxicity to emerging endocrine disruptors through a multiorgan approach

  2025cites this paper
• Reference intervals for serum immunoglobulin A, G, and M in a Danish paediatric population-based cohort.

  2025cites this paper
• Identifying critical windows of susceptibility to perinatal lead exposure on child serum vaccine antibody levels.

  2025cites this paper
• Detection and characterization of bovine coronavirus and rotavirus in calves in Ethiopia

  2025cites this paper
• Gut microbiota and immunity in health and diseases: a review

  2024cites this paper
• Immune transcriptomic profile in adult female pigs: dominance status has more influence than environmental enrichment

  2024cites this paper
• Immune Response to the 13-Valent Pneumococcal Conjugate Vaccine is Reduced in Infants Immunized during the Respiratory Viral Season.

  2024cites this paper
• A cross-section study of the comparison of plasma inflammatory cytokines and short-chain fatty acid in patients with depression and schizophrenia

  2024cites this paper
• A new insight of blood vs. buccal DNA methylation in the forensic identification of monozygotic triplets.

  2024cites this paper
• Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice

  2024cites this paper
• Divergent immune profiles in distinct populations - A vietnamese-german comparison

  2024cites this paper
• Revolutionizing adjuvant development: harnessing AI for next-generation cancer vaccines

  2024cites this paper
• Trends in the cytogenetic and immunologic status of healthy persons; Kazakhstan, 2007-2022.

  2024cites this paper
• Microliter Whole Blood Neutrophil Assay Preserving Physiological Lifespan and Functional Heterogeneity

  2024cites this paper
• Establishment of reference values based on influential characteristics of hematopoietic stem cells and immune cell subsets in the bone marrow

  2024cites this paper
• Trained immunity: Perspectives for disease control strategy in marine mollusc aquaculture

  2024cites this paper
• A lifetime perspective on risk factors for cognitive decline with a special focus on early events

  2024cites this paper
• The effect of whole blood logistics on neutrophil non-specific activation and kinetics ex vivo

  2024cites this paper
• Moving toward improved immune checkpoint immunotherapy for advanced prostate cancer

  2024cites this paper
• B cell receptor-induced IL-10 production from neonatal mouse CD19+CD43- cells depends on STAT5-mediated IL-6 secretion

  2023cites this paper
• The DBL-1/TGF-β signaling pathway tailors behavioral and molecular host responses to a variety of bacteria in Caenorhabditis elegans

  2023cites this paper
• Fusaric acid inhibits cell proliferation and downregulates expressions of toll-like receptors pathway genes in Ishikawa endometrial cancer cells.

  2023cites this paper
• In vitro neutrophil functional assay in microliter whole blood for days-long extraction of donor-specific information

  2023cites this paper
• Whole-genome sequencing provides novel insights into the evolutionary history and genetic adaptation of reindeer populations in northern Eurasia

  2023cites this paper
• Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity

  2023cites this paper
• The effect of whole blood logistics on neutrophil non-specific activation and kinetics ex vivo

  2023cites this paper
• DNA methylome profiling of blood to identify individuals in a pair of monozygotic twins

  2023cites this paper
• DYNAMICS OF INDICATORS OF CELLULAR IMMUNITY IN PUPPIES DEPENDING ON THE MULTIPLICITY OF INTRODUCTION THE BIOLOGICAL STIMULUS

  2023cites this paper
• Poverty and Relapse Risk in Children with Acute Lymphoblastic Leukemia: Children's Oncology Group Study AALL03N1 Report.

  2023cites this paper
• Suicide and Inflammation.

  2023cites this paper
• Association between Meteorological Factors and Outpatient Visits for Herpes Zoster in Hefei, China: A Time-Series Analysis

  2023cites this paper
• Molecular and Epigenetics Mechanisms for the Immune Control of Plasmodium Parasites Infection: A Comprehensive Review

  2023cites this paper
• Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia

  2023cites this paper
• HIV-exposed uninfected infants’ immune defects: From pathogen sensing, oxidative burst to antigens responses

  2023cites this paper
• Domestication shapes the pig gut microbiome and immune traits from the scale of lineage to population

  2023cites this paper
• Twenty-first century bioarchaeology: Taking stock and moving forward.

  2022cites this paper
• Hsp70 overexpression in Drosophila hemocytes attenuates benzene‐induced immune and developmental toxicity via regulating ROS/JNK signaling pathway

  2022cites this paper
• One Year in the Extreme Isolation of Antarctica—Is This Enough to Modulate an “Allergic” Sensitization?

  2022cites this paper
• Environmental Conditions in Early Life, Host Defenses, and Disease in Late Life

  2022cites this paper
• Diet and Hygiene in Modulating Autoimmunity During the Pandemic Era

  2022cites this paper
• COVID-19 ‘asymptomatic’ patients: an old wives’ tale

  2022cites this paper
• Determination of consumers’ fresh fruit and vegetable (FFV) purchasing preferences during the Covid-19 pandemic period: the case of Turkey

  2022cites this paper
• Environmental pollution and the immune system

  2022cites this paper
• B cell receptor induced IL-10 production from neonatal CD19+CD43- cells depends on STAT5 mediated IL-6 secretion

  2022cites this paper
• Biology and Natural History of Type 1 Diabetes Mellitus.

  2022cites this paper
• Immune checkpoint inhibitors for the treatment of sepsis:insights from preclinical and clinical development

  2022cites this paper
• Association of immune cell recruitment and BPD development

  2022cites this paper
• Trained immunity of alveolar macrophages requires metabolic rewiring and type 1 interferon signaling

  2022cites this paper
• Association between Peripheral Inflammatory Cytokines and Cognitive Function in Patients with First-Episode Schizophrenia

  2022cites this paper
• A chromosome-level genome assembly and intestinal transcriptome of Trypoxylus dichotomus (Coleoptera: Scarabaeidae) to understand its lignocellulose digestion ability

  2022cites this paper
• Associations between autoimmune dysfunction and pollutants in Akwesasne Mohawk women: Dichlorodiphenyltrichloroethane and polychlorinated biphenyl exposure

  2022cites this paper
• The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota

  2022cites this paper
• Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses.

  2022cites this paper
• Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection

  2022cites this paper
• Infants' diminished response to DTaP vaccine is associated with exposure to organophosphate esters.

  2022cites this paper
• Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers

  2022cites this paper
• Alginate-based bionanocomposites in wound dressings

  2021cites this paper
• Preventing Atopic Diseases During Childhood – Early Exposure Matters

  2021cites this paper
• The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

  2021cites this paper
• High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges

  2021cites this paper
• Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy

  2021cites this paper
• Mesoporous silica nanoparticle: Heralding a brighter future in cancer nanomedicine

  2021cites this paper
• Evaluation of nutritional status in pediatric patients diagnosed with Covid-19 infection

  2021cites this paper
• Environmental risk factors associated with respiratory diseases in children with socioeconomic disadvantage

  2021cites this paper
• Immunomodulatory Effects of Vitamin D Supplementation in a Deficient Population

  2021cites this paper
• Plasmodium falciparum and Helminth Coinfections Increase IgE and Parasite-Specific IgG Responses

  2021cites this paper
• Association of Maternal Influenza Vaccination During Pregnancy With Early Childhood Health Outcomes.

  2021cites this paper
• The role of incretins and incretin-based drugs in autoimmune diseases.

  2021cites this paper
• Maternal exposure to smoking and infant's wheeze and asthma: Japan Environment and Children's Study.

  2021cites this paper
• COVID-19 age-dependent immunology and clinical outcomes: implications for vaccines

  2021cites this paper
• Vaccination as a preventative measure contributing to immune fitness

  2021cites this paper
• Evaluation of the Level of some Immunological Parameters in Patients with Gastrointestinal Disorders Infected with the Blastocystis Hominis Parasite

  2021cites this paper
• Ecological Risks Due to Immunotoxicological Effects on Aquatic Organisms

  2021cites this paper
• The Functional DNA Methylation Signatures Relevant to Altered Immune Response of Neonatal T Cells with l-Arginine Supplementation

  2021cites this paper
• Prevalence, persistence, and genetics of antibody responses to protein toxins and virulence factors

  2021cites this paper
• Assessing the safety of bioactive ingredients in infant formula that affect the immune system: Recommendations from an expert panel.

  2021cites this paper
• MODIFICATION OF IMMUNOCYTES VIABLE PARAMETERS IN CHILDREN ASSOCIATED WITH COMBINED EXPOSURE TO CHEMICAL TECHNOGENIC AND EXTREME CLIMATIC FACTORS

  2021cites this paper
• Perfluoroalkyl substances exposure and immunity, allergic response, infection, and asthma in children: review of epidemiologic studies

  2021cites this paper
• Detailed Analysis of Immune Tolerance Mechanisms to SARS-CoV-2 in Children Is Needed

  2021cites this paper
• Immunological Trajectories of White Blood Cells from Adolescence to Adulthood: Description and Determinants

  2021cites this paper