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.

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    • "In higher vertebrates, it has been reported that soon after birth more than 50% of all human neonates develop a prominent but transitory rash caused by reaction of the immature skin to commensal flora. Emerging evidence indicates that such bacterial skin interaction may activate the release of IL-6 by the host, which probably contributes to ameliorating the rash, exemplifying how important an appropriate innate immune response against a particular stimulus is required upon maturation of the neonatal immune system (Levy, 2007). These evidences clearly illustrate part of the related mechanism. "
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    ABSTRACT: To grant survival against sterile or microbe induced inflammation, all animals rely on correct immune system functioning. The development of immunity occurs in vertebrates during embryogenesis in a process called hematopoiesis, which is characterized by the formation of blood cellular components such as embryonic erythrocytes and primitive macrophages. These cells are formed in a sterile environment from a rare subset of pluripotent hematopoietic stem cells (HSC) during a brief period of the primitive hematopoietic wave. Diverse signals, like Notch, are indispensable in HSC emergence and differentiation. However, to successfully replicate the process in vitro using pluripotent precursors, the full set of required signals is still a matter of debate. Among the latest findings, proinflammatory signals produced by transient primitive myelocites in zebrafish have been seen to act as essential mediators in establishing the HSC program of the adult vertebrate hematopoietic system. In this regard, the zebrafish immune model has emerged as a feasible live vertebrate model for examining developmental immunity and related host-microbe interactions, both at the molecular and cellular level. Thus, using the zebrafish embryo, this review summarizes recent findings, on the signals required for immune development and further maturation of the system, in a context where no adaptive immune response has yet been developed.
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    • "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. "
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    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.
    Full-text · Article · Feb 2015 · Epidemics
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    • "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. "
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    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.
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