Levy, O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol 7, 379-390

Department of Medicine, Division of Infectious Diseases, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 06/2007; 7(5):379-90. DOI: 10.1038/nri2075
Source: PubMed


The fetus and newborn face a complex set of immunological demands, including protection against infection, avoidance of harmful inflammatory immune responses that can lead to pre-term delivery, and balancing the transition from a sterile intra-uterine environment to a world that is rich in foreign antigens. These demands shape a distinct neonatal innate immune system that is biased against the production of pro-inflammatory cytokines. This bias renders newborns at risk of infection and impairs responses to many vaccines. This Review describes innate immunity in newborns and discusses how this knowledge might be used to prevent and treat infection in this vulnerable population.

Download full-text


Available from: Ofer Levy,
  • Source
    • "This age-dependence is due to two additive phenomena. First, age has a 'biological' effect as host behaviors and immune defenses may evolve with age (e.g., (Anderson et al., 1992; Gasparoni et al., 2003; Levy, 2007; Bogaards et al., 2010)). Second, older individuals are more likely to be seropositive because of a longer exposure time, mechanically creating a cumulative effect of age. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Parasite interactions have been widely evidenced experimentally but field studies remain rare. Such studies are essential to detect interactions of interest and access (co)infection probabilities but face methodological obstacles. Confounding factors can create statistical associations, i.e. false parasite interactions. Among them, host age is a crucial covariate. It influences host exposition and susceptibility to many infections, and has a mechanical effect, older individuals being more at risk because of a longer exposure time. However, age is difficult to estimate in natural populations. Hence, one should be able to deal at least with its cumulative effect. Using a SI type dynamic model, we showed that the cumulative effect of age can generate false interactions theoretically (deterministic modeling) and with a real dataset of feline viruses (stochastic modeling). The risk to wrongly conclude to an association was maximal when parasites induced long-lasting antibodies and had similar forces of infection. We then proposed a method to correct for this effect (and for other potentially confounding shared risk factors) and made it available in a new R package, Interatrix. We also applied the correction to the feline viruses. It offers a way to account for an often neglected confounding factor and should help identifying parasite interactions in the field, a necessary step towards a better understanding of their mechanisms and consequences. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Epidemics 02/2015; 28. DOI:10.1016/j.epidem.2015.02.004 · 1.87 Impact Factor
  • Source
    • "The maturation of the immune system is complex because the multiple component have different ontogenetic trajectories and because they are influenced by both internal factors [e.g., innate immunity; (Cuadros & Navascues, 1998; Levy, 2007)] and external factors [e.g., transmission to the infant via the mother (Newburg & Walker, 2007; Paramasivam, Michie, Opara, & Jewell, 2006)]. Here, we briefly summarize some of those factors as they change during early development. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pain is a serious problem for infants and children and treatment options are limited. Moreover, infants born prematurely or hospitalized for illness likely have concurrent infection that activates the immune system. It is now recognized that the immune system in general and glia in particular influence neurotransmission and that the neural bases of pain are intimately connected to immune function. We know that injuries that induce pain activate immune function and suppressing the immune system alleviates pain. Despite this advance in our understanding, virtually nothing is known of the role that the immune system plays in pain processing in infants and children, even though pain is a serious clinical issue in pediatric medicine. This brief review summarizes the existing data on immune-neural interactions in infants, providing evidence for the immaturity of these interactions. © 2014 Wiley Periodicals, Inc. Dev Psychobiol.
    Developmental Psychobiology 12/2014; 56(8). DOI:10.1002/dev.21229 · 3.31 Impact Factor
  • Source
    • "Il est largement e ´tabli que tous ces mécanismes cellulaires, aptes a ` assurer cette réponse immunitaire du chorion sousmuqueux intestinal, ne sont pas absents chez le jeune nourrisson mais qu'ils sont encore immatures [9] [26] [33]. Les récepteurs dendritiques CD103 + , plus aptes a ` favoriser la réponse de tolérance de la CD, et donc a ` orienter le lymphocyte CD4 + naı¨f dans sa transformation en cellule iTreg, sont encore immatures [26]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Immune deviations have been shown to exponentially increase in young children. As a consequence, research investigating possible environmental reasons for this increase is considered a public health priority. An improved understanding of the immunity of the intestinal submucosal lamina propria has demonstrated the importance of prostaglandins (PGE2s) on its local development with general immune consequences further on. PGE2s appear at this intestinal submucosal level from the metabolism of arachidonic acid mediated by type-2 cyclooxygenases (COX2s) situated in the membranes of many immune cells. The potential risk of repeated inhibition of PGE2 synthesis at a young age has been demonstrated in experiments with animals systemically exposed to a non-steroidal anti-inflammatory drug (NSAID). The repeatedly exposed animal cannot develop tolerance to food antigens and exhibits autoimmune deviations. Acetaminophen (paracetamol) and ibuprofen are analgesic and antipyretic medications given to children either alone or in combination, most often without medical prescription. Recently, it has been demonstrated that paracetamol, like ibuprofen, also carries, besides its central action, a non-selective inhibitory action on peripheral COXs. However, this inhibitory action ordy relates to physiological concentrations of arachidonic acid and explains the difference in their respective anti-inflammatory effects. Since recently published data have repeatedly reported an increase of immune deviations associated with paracetamol exposure at a young age, it appears important to better understand the possible negative impact of excessive and repetitive inhibitions of the physiological synthesis of piostaglandins by COX2s in childhood during which all immune mechanisms are built up at the intestinal submucosal level. Therefore, a well-designed prospective strategy for pharmacovigilance of these COX inhibitors repeatedly given during childhood is urgently needed.
    Archives de Pédiatrie 11/2014; 22(3). DOI:10.1016/j.arcped.2014.11.003 · 0.41 Impact Factor
Show more