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      HIV-exposed uninfected infants’ immune defects: From pathogen sensing, oxidative burst to antigens responses

      review-article
      1 , 2 , , 1 , 2
      iScience
      Elsevier
      Immunology, Virology

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          Summary

          The progress in preventing mother-to-child transmission of HIV has led to a significant reduction in mother-to-child HIV transmission, increasing the population of HIV-exposed uninfected (HEU) infants. Studies have shown that HEU infants are more vulnerable to diseases than infants born from HIV-free mothers. Today, there is more and more evidence that helps us understand how exposure to HIV and/or its therapy affects the ability of the immune system of HEU infants to fight infections. This paper mapped out reported critical immune defects in HEU infants, from pathogen sensing and recognition, oxidative burst to antigens-specific responses. Models of neutrophils and monocyte malfunctions in these infants are proposed.

          Abstract

          Immunology; Virology

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          Most cited references55

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          Pathogen recognition and inflammatory signaling in innate immune defenses.

          The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.
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            Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000.

            Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in 2010 with time trends since 2000. Updated total numbers of deaths in children aged 0-27 days and 1-59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1-59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates. Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range [UR] 0·916-1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610-0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252-0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977-1·176), diarrhoea (9·9%; 0·751 million, 0·538-1·031), and malaria (7·4%; 0·564 million, 0·432-0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million [0·339-0·547], 0·363 million [0·283-0·419], and 0·359 million [0·215-0·476], respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4. Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010-15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates. The Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Developmental and Functional Heterogeneity of Monocytes

              Novel experimental approaches such as fate-mapping and single-cell analysis have brought fresh insight into monocyte development and function over the past decade and helped redefine the monocyte field. Monocytes are now known to consist of multiple subsets generated through distinct developmental pathways with diverse functional specializations. Their fates under homeostatic conditions include the accumulation in peripheral reservoirs and the engraftment into certain resident macrophage pools. Under pathological conditions, monocytes acquire inflammatory effector functions, but can also develop regulatory properties essential for tissue repair. Importantly, monocytes recruited during inflammation are often functionally distinct from resident macrophages or conventional dendritic cells. Here we outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity and discuss how these bring new perspectives to monocyte research.
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                Author and article information

                Contributors
                Journal
                iScience
                iScience
                iScience
                Elsevier
                2589-0042
                10 November 2023
                15 December 2023
                10 November 2023
                : 26
                : 12
                : 108427
                Affiliations
                [1 ]Service Laboratoire Centre Hospitalier Universitaire Mère-Enfant, Fondation Jeanne EBORI, Libreville, Gabon
                [2 ]Unité de Recherche et de Diagnostics Spécialisés, Laboratoire National de Santé Publique, Libreville, Gabon
                Author notes
                []Corresponding author joel.djoba@ 123456gmail.com
                Article
                S2589-0042(23)02504-X 108427
                10.1016/j.isci.2023.108427
                10708997
                38077134
                9c6efeab-00d8-4532-8755-3f4ac92e4f50
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                immunology,virology
                immunology, virology

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