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Immunology response neonates

Jennifer R Bermick, Nathalie J Lambrecht, Aaron D denDekker, Steven L Kunkel, Nicholas W Lukacs, Cory M Hogaboam, Matthew A Schaller
BACKGROUND: Neonates have dampened expression of pro-inflammatory cytokines and difficulty clearing pathogens. This makes them uniquely susceptible to infections, but the factors regulating neonatal-specific immune responses are poorly understood. Epigenetics, including histone modifications, can activate or silence gene transcription by modulating chromatin structure and stability without affecting the DNA sequence itself and are potentially modifiable. Histone modifications are known to regulate immune cell differentiation and function in adults but have not been well studied in neonates...
2016: Clinical Epigenetics
Bettina Mavrommatis, Lucie Baudino, Prisca Levy, Julia Merkenschlager, Urszula Eksmond, Tiziano Donnarumma, George Young, Jonathan Stoye, George Kassiotis
Elucidation of the immune requirements for control or elimination of retroviral infection remains an important aim. We studied the induction of adaptive immunity to neonatal infection with a murine retrovirus, under conditions leading to immunological tolerance. We found that the absence of either maternal or offspring adaptive immunity permitted efficient vertical transmission of the retrovirus. Maternal immunodeficiency allowed the retrovirus to induce central Th cell tolerance in the infected offspring. In turn, this compromised the offspring's ability to mount a protective Th cell-dependent B cell response...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Filip A Dabrowski, Anna Burdzinska, Agnieszka Kulesza, Marcin Chlebus, Beata Kaleta, Jan Borysowski, Aleksandra Zolocinska, Leszek Paczek, Miroslaw Wielgos
BACKGROUND/AIM: Mesenchymal stem cells (MSCs) are gaining rising interest in gynecology and obstetrics. MSCs immunomodulatory properties are suitable enough to reduce perinatal morbidity caused by inflammation in premature neonates. The aim of this study was to evaluate and compare the ability to inhibit allo-activated lymphocytes proliferation by MSCs derived from different sources: amniotic membrane (AM), umbilical cord (UC) and adipose tissue (AT). METHODS: MSCs were isolated from AM (n = 7) and UC (n = 6) and AT (n = 6) of healthy women...
September 15, 2016: Gynecologic and Obstetric Investigation
T Sun, O L Rojas, C Li, L A Ward, D J Philpott, J L Gommerman
Although we know a great deal about which types of dendritic cells (DCs) promote T-cell priming in the periphery, less is known about which DC subset(s) provoke antiviral responses within the gut. Here we report that conventional Zbtb46-dependent DCs were critically required for antiviral CD8(+) T-cell responses against rotavirus (RV), the major cause of childhood gastroenteritis worldwide. Furthermore, we found that in adult mice, Batf3-dependent DCs were required for generating optimal RV-specific CD8(+) T-cell responses...
September 7, 2016: Mucosal Immunology
Wei Wang, Li Xue, Tongsheng Ma, Yuan Li, Zhenguang Li
The pathogenesis of necrotizing enterocolitis (NEC) is not well understood but immunological factors are thought to be key determinants of the disease appearance and its prognosis. During the course of the present study, different groups of newborn infants were observed and tested, to obtain an accurate image of values of pro- and anti-inflammatory cytokines at the onset, development and progression of neonatal NEC and to compare the values to those obtained during normal healthy development. All the infants in the study received standard medical treatment as appropriate...
September 2016: Experimental and Therapeutic Medicine
Derek Dc Ireland, Cecilia Tami, Joao Pedras-Vasconcelos, Daniela Verthelyi
Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central nervous system (CNS) while minimizing neuron damage remains a critical challenge. Neonatal mice inoculated intraperitoneally with Tacaribe virus (TCRV) develop seizures, hindlimb paralysis and death within 15 days of inoculation...
August 29, 2016: Cellular & Molecular Immunology
Sara Manti, Lucia Marseglia, Gabriella D'Angelo, Caterina Cuppari, Erika Cusumano, Teresa Arrigo, Eloisa Gitto, Carmelo Salpietro
Although extensive epidemiological and laboratory studies have been performed to identify the environmental and immunological causes of atopy, genetic predisposition seems to be the biggest risk factor for allergic diseases. The onset of atopic diseases may be the result of heritable changes of gene expression, without any alteration in DNA sequences occurring in response to early environmental stimuli. Findings suggest that the establishment of a peculiar epigenetic pattern may also be generated by oxidative stress (OS) and perpetuated by the activation of OS-related genes...
2016: Oxidative Medicine and Cellular Longevity
David Liuwantara, Yi Vee Chew, Emmanuel J Favaloro, Joanne M Hawkes, Heather L Burns, Philip J O'Connell, Wayne J Hawthorne
INTRODUCTION: The instant blood-mediated inflammatory reaction (IBMIR) causes major loss of islets after transplantation and consequently represents the initial barrier to survival of porcine neonatal islet cell clusters (NICC) after xenotransplantation. METHODS: This study used novel assays designed to characterize the various immunologic components responsible for xenogeneic IBMIR to identify initiators and investigate processes of IBMIR-associated coagulation, complement activation and neutrophil infiltration...
June 2016: Transplantation Direct
Ryan S Doster, Leslie Kirk, Lauren M Tetz, Lisa M Rogers, David M Aronoff, Jennifer A Gaddy
Staphylococcus aureus, a metabolically flexible, Gram-positive pathogen, causes infections in a variety of tissues. Recent evidence implicates S. aureus as an emerging cause of chorioamnionitis and premature rupture of membranes, which are associated with preterm birth and neonatal disease. We demonstrate here that S. aureus infects and forms biofilms on the choriodecidual surface of explanted human gestational membranes. Concomitantly, S. aureus elicits the production of proinflammatory cytokines, which could ultimately perturb maternal-fetal tolerance during pregnancy...
July 19, 2016: Journal of Infectious Diseases
Gianluca Picariello, Francesco Addeo, Pasquale Ferranti, Rita Nocerino, Lorella Paparo, Annalisa Passariello, David C Dallas, Randall C Robinson, Daniela Barile, Roberto Berni Canani
Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow's milk allergy. However, the definite characterization of dietary cow's milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. Herein, we aimed at assessing possible CMP-derived peptides in breast milk. Using high performance liquid chromatography (HPLC)-high resolution mass spectrometry (MS), we compared the peptide fraction of breast milk from 12 donors, among which 6 drank a cup of milk daily and 6 were on a strict dairy-free diet...
August 10, 2016: Food & Function
Nicole Ritz, Dan Casalaz, Susan Donath, Marc Tebruegge, Binita Dutta, Tom G Connell, Roy Robins-Browne, Warwick J Britton, Willem A Hanekom, Nigel Curtis
BACKGROUND: More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia...
July 29, 2016: Vaccine
Christian Hinderer, Peter Bell, Jean-Pierre Louboutin, Nathan Katz, Yanqing Zhu, Gloria Lin, Ruth Choa, Jessica Bagel, Patricia O'Donnell, Caitlin A Fitzgerald, Therese Langan, Ping Wang, Margret L Casal, Mark E Haskins, James M Wilson
High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme α-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I...
September 2016: Molecular Genetics and Metabolism
R Linsingen, M G Bicalho, N S Carvalho
Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, immunological factors also appear to be involved. Recently, molecular genetic studies have helped us better understand the underlying pathophysiologic processes...
July 5, 2016: Journal of Maternal-fetal & Neonatal Medicine
Eui-Cheol Shin, Pil Soo Sung, Su-Hyung Park
Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection...
August 2016: Nature Reviews. Immunology
E Stein Esser, AndreyA Romanyuk, Elena V Vassilieva, Joshy Jacob, Mark R Prausnitz, Richard W Compans, Ioanna Skountzou
Maternal and neonatal tetanus claim tens of thousands lives every year in developing countries, but could be prevented by hygienic practices and improved immunization of pregnant women. This study tested the hypothesis that skin vaccination can overcome the immunologically transformed state of pregnancy and enhance protective immunity to tetanus in mothers and their newborns. To achieve this goal, we developed microneedle patches (MNPs) that efficiently delivered unadjuvanted tetanus toxoid to skin of pregnant mice and demonstrated that this route induced superior immune responses in female mice conferring 100% survival to tetanus toxin challenge when compared to intramuscular vaccination...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Enrique Segura-Cervantes, Javier Mancilla-Ramírez, Jorge González-Canudas, Erika Alba, René Santillán-Ballesteros, Deneb Morales-Barquet, Gabriela Sandoval-Plata, Norma Galindo-Sevilla
The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry...
2016: Mediators of Inflammation
F Al-Saif, A Elisa, A Al-Homidy, A Al-Ageel, M Al-Mubarak
BACKGROUND AND OBJECTIVES: Pemphigoid gestationis (PG) is a rare autoimmune-mediated blistering disease that mainly affects pregnant women in their 2nd or 3rd trimester and immediate postpartum period. In addition to the clinical assessment, the diagnosis of PG is usually confirmed by histological and immunological studies. PG usually flares up at the time of delivery and spontaneously improves postpartum. Prompt recognition and appropriate management may reduce morbidity associated with this disorder...
August 2016: Journal of Reproductive Immunology
Arnold Reynaldi, Norah L Smith, Timothy E Schlub, Vanessa Venturi, Brian D Rudd, Miles P Davenport
Neonates are particularly susceptible to a number of infections, and the neonatal CD8+ T cell response demonstrates differences in both the phenotype and magnitude of responses to infection compared with adults. However, the underlying basis for these differences is unclear. We have used a mathematical modeling approach to analyze the dynamics of neonatal and adult CD8+ T cell responses following in vitro stimulation and in vivo infection, which allows us to dissect key cell-intrinsic differences in expansion, differentiation and memory formation...
May 4, 2016: Immunology and Cell Biology
Nadine van Montfoort, Evelyn van der Aa, Aniek van den Bosch, Hilde Brouwers, Thomas Vanwolleghem, Harry L A Janssen, Hassan Javanbakht, Sonja I Buschow, Andrea M Woltman
UNLABELLED: Hepatitis B virus (HBV) infection can cause chronic liver disease, which is associated with increased risk of liver cirrhosis, liver failure, and liver cancer. Clearance of HBV infection requires effective HBV-specific immunity; however, the immunological mechanisms that determine the development of effective HBV-specific immunity are poorly understood. Dendritic cells (DC) play a pivotal role in the regulation of antiviral immunity. Here, we investigated the interaction between HBV surface antigen (HBsAg), the main envelope glycoprotein of HBV, and BDCA1(+) myeloid dendritic cells (mDC)...
July 15, 2016: Journal of Virology
Lalit K Beura, Sara E Hamilton, Kevin Bi, Jason M Schenkel, Oludare A Odumade, Kerry A Casey, Emily A Thompson, Kathryn A Fraser, Pamela C Rosato, Ali Filali-Mouhim, Rafick P Sekaly, Marc K Jenkins, Vaiva Vezys, W Nicholas Haining, Stephen C Jameson, David Masopust
Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside...
April 28, 2016: Nature
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