Dataset Information

Stereotypic Immune System Development in Newborn Children.

ABSTRACT: Epidemiological data suggest that early life exposures are key determinants of immune-mediated disease later in life. Young children are also particularly susceptible to infections, warranting more analyses of immune system development early in life. Such analyses mostly have been performed in mouse models or human cord blood samples, but these cannot account for the complex environmental exposures influencing human newborns after birth. Here, we performed longitudinal analyses in 100 newborn children, sampled up to 4 times during their first 3 months of life. From 100 ?L of blood, we analyze the development of 58 immune cell populations by mass cytometry and 267 plasma proteins by immunoassays, uncovering drastic changes not predictable from cord blood measurements but following a stereotypic pattern. Preterm and term children differ at birth but converge onto a shared trajectory, seemingly driven by microbial interactions and hampered by early gut bacterial dysbiosis.

SUBMITTER: Olin A

PROVIDER: S-EPMC6108833 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Stereotypic Immune System Development in Newborn Children.

Olin Axel A Henckel Ewa E Chen Yang Y Lakshmikanth Tadepally T Pou Christian C Mikes Jaromir J Gustafsson Anna A Bernhardsson Anna Karin AK Zhang Cheng C Bohlin Kajsa K Brodin Petter P

Cell 20180801 5

Epidemiological data suggest that early life exposures are key determinants of immune-mediated disease later in life. Young children are also particularly susceptible to infections, warranting more analyses of immune system development early in life. Such analyses mostly have been performed in mouse models or human cord blood samples, but these cannot account for the complex environmental exposures influencing human newborns after birth. Here, we performed longitudinal analyses in 100 newborn ch ...[more]

PMID: 30142345

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Project description:BackgroundPublic health surveillance is crucial in monitoring the progress of maternal, newborn, and children under-five health outcomes (MNCH). Consequently, mapping the existing surveillance system from countries with different income and development levels is needed to learn and compare the effectiveness of surveillance. However, the current COVID-19 pandemic has disrupted the health system, including the healthcare services for pregnant women, neonates, infants, and children under five, as well as the recording, reporting, and surveillance system. The need to adapt to the new normal during the pandemic has stimulated innovation while incorporating new COVID-19-related indicators into the existing public health system. Therefore, this review aims to describe the existing implementation and the COVID-19 pandemic's influence on the MNCH surveillance system.MethodsWe will search published literature (from MEDLINE, Embase, and Portal Garuda), manually search from all reference lists of included studies, and conduct a targeted search of relevant gray literature. This review will include studies of surveillance systems or describe COVID-19 surveillance or routine reports involving MNCH (morbidity and mortality). The studies included will be in English or Indonesian language, observational study designs, and published or documented from 2010 to 2023. Two investigators will independently screen the title and abstract, including each full article to determine the eligibility of studies. The data will be assessed using a narrative approach. Data will be reported in simple descriptive tables.DiscussionOur findings are expected to map the existing implementation of MNCH surveillance systems before and during the pandemic, including the influence of the COVID-19 pandemic on MNCH surveillance across countries with different income levels. This may contribute to existing knowledge on the MNCH health surveillance system that could be integrated into the surveillance of emerging diseases, such as COVID-19.Systematic review registrationThe protocol has been registered on the Open Science Framework ( https://osf.io/bc6t4 ).

Project description:BACKGROUND:Oligoadenylate synthetases (OASs) are widely distributed in Metazoa including sponges, fish, reptiles, birds and mammals and show large variation, with one to twelve members in any given species. Upon double-stranded RNA (dsRNA) binding, avian and mammalian OASs generate the second messenger 2'-5'-linked oligoadenylate (2-5A), which activates ribonuclease L (RNaseL) and blocks viral replication. However, how Metazoa shape their OAS repertoires to keep evolutionary balance to virus infection is largely unknown. We performed comprehensive phylogenetic and functional analyses of OAS genes from evolutionarily lower to higher Metazoa to demonstrate how the OAS repertoires have developed anti-viral activity and diversified their functions. RESULTS:Ancient Metazoa harbor OAS genes, but lack both upstream and downstream genes of the OAS-related pathways, indicating that ancient OASs are not interferon-induced genes involved in the innate immune system. Compared to OASs of ancient Metazoa (i.e. sponge), the corresponding ones of higher Metazoa present an increasing number of basic residues on the OAS/dsRNA interaction interface. Such an increase of basic residues might improve their binding affinity to dsRNA. Moreover, mutations of functional residues in the active pocket might lead to the fact that higher Metazoan OASs lose the ability to produce 3'-5'-linked oligoadenylate (3-5A) and turn into specific 2-5A synthetases. In addition, we found that multiple rounds of gene duplication and domain coupling events occurred in the OAS family and mutations at functionally critical sites were observed in most new OAS members. CONCLUSIONS:We propose a model for the expansion of OAS members and provide comprehensive evidence of subsequent neo-functionalization and sub-functionalization. Our observations lay the foundation for interrogating the evolutionary transition of ancient OAS genes to host defense genes and provide important information for exploring the unknown function of the OAS gene family.

Project description:BackgroundMalnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed.ObjectivesTo review the scientific literature about immune function in children with malnutrition.MethodsA systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1-60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition.ResultsThe literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied.ConclusionThe immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.

Dataset Information

Stereotypic Immune System Development in Newborn Children.

Publications

Stereotypic Immune System Development in Newborn Children.

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