Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults

Despite significant progress in reducing the burden of mortality in children under the age of five, reducing mortality in newborns remains a major challenge. Infection plays a significant role in infant deaths and interventions such as early vaccination or antenatal immunization could make a significant contribution to prevention of such deaths. In the last few years, we have gained new insights into immune ontogeny and are now beginning to understand the impact of vaccines, nutrition and environmental factors on ‘training′ of the immune response in early life. This review article sets out to explain why vaccine responses can be heterogeneous between populations and individuals by providing examples chosen to illustrate the impact of host, pathogen and environmental factors on shaping the immune ‘interactome′ in young children.

show abstract

“…Similar data were reported from Papua New Guinea and across a number of countries using comparable methodology [10][11][12].…”

Section: Introductionsupporting

confidence: 65%

Factors influencing innate immunity and vaccine responses in infancy

Kampmann

Jones

2015

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

show abstract

“…For example, bloodderived monocytes from human infants have reduced production of cytokines such as IFNa, IFNg and IL-12, upon toll-like receptor (TLR) stimulation, but have an increase in IL-10 and the T helper (Th)17-inducing cytokines, IL-6 and IL-23. 4 Antiviral cytokines, such as type I IFNs are protective in young children. For example, susceptibility to severe herpes simplex virus (HSV) infection correlates with low TLR-mediated type I IFN production in children 5 In addition to the direct antiviral mechanisms, inflammatory cytokines triggered through innate receptors also control the differentiation of the adaptive immune response and memory development.…”

Section: Neonatal Innate Immunitymentioning

confidence: 99%

Vaccination and heterologous immunity: educating the immune system

Gil¹,

Kenney²,

Mishra³

et al. 2015

Transactions of the Royal Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. This leads to the question, is there an optimum way to educate the immune system? Should this be taken into consideration in our vaccination protocols?

show abstract

“…These cells have been shown to react differently compared with peripheral blood monocytes of adults. Affected are qualitative and quantitative phagocytic capacities and impaired responses upon different stimulating agents [6][7][8][9]. Until now, neonatal monocytes and macrophages have been described as immature or dormant myeloid cells.…”

Section: Introductionmentioning

confidence: 99%

“…Although maternal antibodies help the neonate in the first weeks, it has to develop its own adaptive immune capacities during infancy [2]. In the neonatal period, monocytes and [6][7][8][9]. Until now, neonatal monocytes and macrophages have been described as immature or dormant myeloid cells.…”

mentioning

confidence: 99%

Distinct phenotypic features of neonatal murine macrophages

et al. 2014

View full text Add to dashboard Cite

Neonates rely on their innate immune system. Resident tissue macrophages are considered to be initiators and regulators of the innate immune response and thus, appear to be especially important to neonates. We hypothesized that the phenotype and function of neonatal tissue macrophages differ from their adult counterparts. Peritoneal macrophages from neonatal (<24 h) and adult (6 weeks old) C57BL/6J mice were isolated and analyzed by high-content chipcytometry. After stimulation for 6 h with LPS (0, 1, 10, 100 ng/mL), macrophage transcriptome was analyzed by microarray and cytokine release was measured using multiparametric bead assays. Antigen presenting capacity was compared by T-cell stimulation assays. We observed that neonatal murine peritoneal macrophages are characterized by selective lack of expression of F4/80, MHC class II, and costimulatory molecules (CD80, CD86). Furthermore, we found differences in the transcriptome between neonatal and adult macrophages, unstimulated and after LPS stimulation. Although neonatal macrophages showed a significantly increased secretion of proinflammatory cytokines upon LPS stimulation, their potential to induce T-cell proliferation was significantly reduced. In conclusion, we observed a distinct phenotype of the neonatal macrophage population. The specific functions of this macrophage population could help to understand the excessive inflammatory reactions observed in the very young.Keywords: Immune responses r Macrophages r Neonate immunity r Toll-like receptors (TLRs) Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNeonates and in particular preterm infants are extremely vulnerable to states of inflammation [1]. They have an increased susceptibility to microbial infections with an enhanced morbidity and Correspondence: Mr. Thomas Winterberg e-mail: Winterberg.thomas@mh-hannover.de mortality [2]. Sepsis, pneumonia, and gastrointestinal disorders such as necrotizing enterocolitis are a common threat to patients in neonatal intensive care. The first days of life represent a period of transition of the immune system: The protection of the fetus by the maternal immune system and the sterile environment are lost and the newborn has to cope with the outside world and its multiple foreign antigens. Although maternal antibodies help the neonate in the first weeks, it has to develop its own adaptive immune capacities during infancy [2]. In the neonatal period, monocytes and [6][7][8][9]. Until now, neonatal monocytes and macrophages have been described as immature or dormant myeloid cells. However, these studies are based on peripheral blood monocytes or CBMs, which further differentiate into macrophages ex vivo. Little is known about tissue macrophages in neonates, due to technical difficulties of their isolation and evaluation, but a recent study demonstrated their unique function during heart tissue regeneration [10].It has been shown that the heterogeneous murine macrophage populations are orig...

show abstract

Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults

Cited by 413 publications

References 43 publications

Factors influencing innate immunity and vaccine responses in infancy

Factors influencing innate immunity and vaccine responses in infancy

Vaccination and heterologous immunity: educating the immune system

Distinct phenotypic features of neonatal murine macrophages

Contact Info

Product

Resources

About