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Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny
Open accessAbstract
Infections in the first year of life are common and often severe. The newborn host demonstrates both quantitative and qualitative differences to the adult in nearly all aspects of immunity, which at least partially explain the increased susceptibility to infection. Here we discuss how differences in susceptibility to infection result not out of a state of immaturity, but rather reflect adaptation to the particular demands placed on the immune system in early life. We review the mechanisms underlying host defense in the very young, and discuss how specific developmental demands increase the risk of particular infectious diseases. In this context, we discuss how this plasticity, i.e. the capacity to adapt to demands encountered in early life, also provides the potential to leverage protection of the young against infection and disease through a number of interventions.
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“Vaccination early in life, as well as exposure to a variety of immunogens, can also affect response to pathogens and vaccines across the lifespan, sometimes in unpredictable ways.23”
From SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges (2021) · cites this paper as [23]
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“In conclusion, our in-depth analysis of the kinetics of MAIT cell development and its correlation with microbial or nonmicrobial environmental exposures highlights important defects in the newborn, as demonstrated for many other cellular and molecular components of innate immune responses (Kollmann et al., 2017).”
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Breastmilk cell trafficking induces microchimerism‐mediated immune system maturation in the infant
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“Time elapsed between waking up and milk sampling (min) Week 2 30.00 (8.58–51.40) 63.40 (17.10–110.00) 0.178 Week 6 45.40 (15.20–75.60) 154.00 (27.10–281.00) 0.055 Week 12 24.70 (2.05–47.40) 153.00 (27.40–278.00) 0.046 a t-tests were used to evaluate differences between both groups at each postnatal week. https://doi.o…”
BackgroundResultInfluentialPerinatal development of innate immune topology
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“, TNFa, IL-6, and IL-10), yet respond weakly with type I interferons to cytomegalovirus infection (Kollmann et al., 2017).”
BackgroundInfluentialInnate Immunity to Respiratory Infection in Early Life
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Self-citationElahi, S., Vega‐López, M. A., Herman-Miguel, V., Ramírez-Estudillo, C., Mancilla-Ramı́rez, J., Motyka, B., West, L. J., & Oyegbami, O. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.597433 · Cited by 57
Preterm neonatal immunology at the intestinal interface
Belkum, M. V., Alvarez, L. M., & Neu, J. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03316-w · Cited by 59
Cooper, D. M., Afghani, B., Byington, C. L., Cunningham, C. K., Golub, S., Lu, K. D., Radom-Aizik, S., Ross, L. F., Singh, J., Smoyer, W. E., et al. (2021) · Pediatric Research · doi:10.1038/s41390-021-01402-z · Cited by 55
COVID-19 Vaccination in Pregnancy and Lactation: Current Research and Gaps in Understanding
Shook, L. L., Fallah, P. N., Silberman, J. N., & Edlow, A. G. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.735394 · Cited by 59
“…data investigating the vaccine-induced cellular and serological immune response in individuals previously infected with SARS-CoV-2 points to a robust response to the first vaccine dose in both circulating antibodies and antigen-specific memory B cells (Goel et al., 2021; Krammer et al., 2021).”
BackgroundWang, J., Cao, H., Sun, D., Qi, Z., Guo, C., Peng, W., Sun, Y., Xie, Y., Liu, X., Li, B., et al. (2019) · Environmental Research · doi:10.1016/j.envres.2019.108531 · Cited by 54
“Infants have more immature immune systems and little immunological memory (Basha et al., 2014; Kollmann et al., 2017), resulting in slower inflammatory responses and autoimmune injuries versus those of older children.”
BackgroundSeal, S. V., & Turner, J. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073344 · Cited by 61
Maternal Immunization: Nature Meets Nurture
Saso, A., & Kampmann, B. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01499 · Cited by 53
Self-citationNeonatal Immunization: Rationale, Current State, and Future Prospects
Whittaker, E., Goldblatt, D., McIntyre, P. B., & Levy, O. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00532 · Cited by 53
Self-citationTropism of SARS-CoV-2 for Developing Human Cortical AstrocytesPreprint
Andrews, M. G., Mukhtar, T., Eze, U. C., Simoneau, C. R., Perez, Y., Mostajo-Radji, M. A., Wang, S., Velmeshev, D., Salma, J., Kumar, G. R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.17.427024 · Cited by 51
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“Several components of the innate immune system are being developed early in life but can take until the teenage years to become fully developed (Ygberg and Nilsson 2012; Kollmann et al. 2017).”
BackgroundB Regulatory Cells: Players in Pregnancy and Early Life
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“Although the neonate’s immune system can fight pathogen infections, as a result of the need of tolerance, there is an increased risk for severe infections [25].”
BackgroundPerinatal development of innate immune topology
Henneke, P., Kierdorf, K., Hall, L. J., Sperandio, M., & Hornef, M. W. (2021) · RWTH Publications (RWTH Aachen) · Cited by 45
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Self-citationLandscape and age dynamics of immune cells in the Egyptian rousette bat
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Enamel opacities in all other than Molar Incisor Hypomineralisation index teeth of adolescents
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Self-citationImpact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming
Sureshchandra, S., Marshall, N., & Messaoudi, I. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ri0619-181r · Cited by 38
Cellular metabolism constrains innate immune responses in early human ontogeny
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Self-citationVascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities
Pietrasanta, C., Pugni, L., Ronchi, A., Bottino, I., Ghirardi, B., Sánchez‐Schmitz, G., Borriello, F., Mosca, F., & Levy, O. (2019) · Frontiers in Pediatrics · doi:10.3389/fped.2019.00340 · Cited by 39
“e) The influence of distinctive immunomodulatory blood components, such as maternal antibodies, high concentrations of adenosine, and reduced concentrations of complement (4, 8).”
BackgroundSelf-citationA perfect storm: fetal inflammation and the developing immune system
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The effect of maternal antibodies on the cellular immune response after infant vaccination: A review
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“However, as the first 6 months of life are characterized by vital immunological changes, such as Th1-Th2 cytokine and effector/ regulatory T cell stasis refinement [21,48,49], there is no doubt that future research should include extensive analyses of the CMI responses at young age.”
BackgroundInfluentialSkin Barrier Function in Neonates and Infants
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“The negative correlation of Treg frequency and gestational age within the first 21 days of life (Supplementary Table 1 and Supplementary Figure 2) underlines the potential role of fetal Tregs to promote self-tolerance and tolerance to maternal antigens (17, 26, 51).”
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“Based on recent developments in the neonatal immunology field (1, 4, 5, 54, 75), the choice of immune response against COVID-19 in children and adolescents versus adults may serve as an explanation for the observed differential clinical outcomes.”
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“Hence, newborns present a particular immune response that relates to the unique environmental pressures and challenges of the first days of life [65,66].”
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Surfing on the waves of the human γδ T cell ontogenic sea
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Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance
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Sánchez‐Schmitz, G., Stevens, C. R., Bettencourt, I. A., Flynn, P. J., Schmitz‐Abe, K., Metser, G., Hamm, D. E., Jensen, K. J., Benn, C. S., & Levy, O. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02634 · Cited by 36
“Moreover, comparison of newborn and adult responses demonstrated that multiple aspects of our results also match age-specific differences noted in other human in vitro and in vivo studies (2, 24, 31, 32, 74), suggesting the validity of our approach: (i) greater and broader adult DC maturation and lymphoproliferation t…”
ResultSelf-citationBudeus, B., Kibler, A., Brauser, M., Homp, E., Bronischewski, K., Ross, J. A., Görgens, A., Weniger, M. A., Dunst, J., Kreslavsky, T., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100113 · Cited by 38
Precision Vaccine Development: Cues From Natural Immunity
Barman, S., Soni, D., Brook, B., Nanishi, E., & Dowling, D. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.662218 · Cited by 35
“Firstly, upon pathogen challenge or vaccination, the inability of the neonatal and infant immune system to mount a polyfunctional T helper (Th) polarizing response (10), shifting away from protective Th1 and cytotoxic T cell immunity toward dysregulated Th2 and Th17 polarization (11).”
BackgroundBennike, T. B., Fatou, B., Angelidou, A., Diray‐Arce, J., Falsafi, R., Ford, R. L., Gill, E. E., van Haren, S. D., Idoko, O. T., Lee, A. H., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.578505 · Cited by 34
“Neonatal infections cause 700,000 annual casualties, corresponding to 40% of deaths in children under 5 years of age (2).”
BackgroundSelf-citation
Metadata
- Authors
- Kollmann, T. R., Kampmann, B., Mazmanian, S. K., Marchant, A., & Levy, O.
- Affiliations
- University of British Columbia (CA)
- MRC Unit the Gambia (GM)
- California Institute of Technology (US)
- Université Libre de Bruxelles (BE)
- Boston Children's Hospital (US)
- Corresponding author
- Kollmann, Tobias R.
- Levy, Ofer
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 46
- Issue
- 3
- Pages
- 350-363
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2599501186
- Semantic Scholar
- e51f9b517003c880df24898208e6d4d93bb7cc87
- Cited by
- 478
- References
- 200
- Citations by year
- 2026: 62 · 2025: 45 · 2024: 54 · 2023: 51 · 2022: 40 · 2021: 67 · 2020: 69 · 2019: 39 · 2018: 36 · 2017: 15
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- Medical Research Council (MR/R005990/1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and Maternal Infections
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- immune ontogeny, neonatal immunity, host defense, immune plasticity, neonatal infection
- MeSH terms
- Animals, Communicable Diseases, Disease Susceptibility, Humans, Immune System, Infant, Infant, Newborn
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