PMID- 30909151 OWN - NLM STAT- MEDLINE DCOM- 20200806 LR - 20200806 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 119 DP - 2019 Jul TI - Nucleic acid cytokine responses in obese children and infants of obese mothers. PG - 152-158 LID - S1043-4666(19)30092-4 [pii] LID - 10.1016/j.cyto.2019.03.015 [doi] AB - Almost a third of Irish children are now overweight and the country ranks 58th out of 200 countries for its proportion of overweight youths. With the rising obesity epidemic, and the impaired immune responses of this population, it is vital to understand the effects that obesity has on the immune system and to design future therapeutics, adjuvants and vaccines with overweight and obese populations in mind. Many current vaccines use adjuvants that have been found to be less effective at stimulating the immune response in children compared with adults and there is now substantial effort to design paediatric-focused adjuvants. Additionally, vaccine responses have been shown to be less effective in obese populations indicating that this is a particularly vulnerable population. We have recently identified cytosolic nucleic acids (CNAs), as novel candidate adjuvants for childhood vaccines. Here we investigated whether immune responses to these candidate adjuvants were adversely affected in infants born to overweight or obese mothers, and in overweight and obese children. Type I Interferon (IFN) and proinflammatory cytokines such as Tumor Necrosis Factor alpha (TNFalpha) are vital for driving innate and adaptive immune responses. We found that childhood obesity conferred no significant adverse effect on CNA-induced Type I IFN responses when compared with lean children. Similarly, Type I IFN responses were intact in the cord blood of babies delivered from overweight and obese mothers, when compared with lean mothers. There was also no significant impact of obesity on CNA-induced TNFalpha responses in children or from cord blood of infants born to overweight/obese mothers. In all cases, there was a tendency towards decreased production of innate cytokine Type I Interferon and TNFalpha, however there was no significant negative correlation. Interestingly, high maternal BMI showed weak and moderate positive correlation with IL-12p70 and IFNgamma, respectively, in response to CNA stimulation. This study demonstrates that future adjuvants can be tailored for these populations through the use of activators of CNA sensors. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Brennan, Kiva AU - Brennan K AD - National Children's Research Centre, Crumlin, Dublin 12, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland. FAU - O'Leary, Bobby D AU - O'Leary BD AD - UCD Perinatal Research Centre, Obstetrics & Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland. FAU - Mc Laughlin, Danielle AU - Mc Laughlin D AD - Department of Paediatric Surgery, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. FAU - Kinlen, David AU - Kinlen D AD - National Children's Research Centre, Crumlin, Dublin 12, Ireland; Department of Diabetes and Endocrinology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. FAU - Molloy, Eleanor J AU - Molloy EJ AD - National Children's Research Centre, Crumlin, Dublin 12, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland; Coombe Women and Infants University Hospital, Dublin 8, Ireland. FAU - Cody, Declan AU - Cody D AD - National Children's Research Centre, Crumlin, Dublin 12, Ireland; Department of Diabetes and Endocrinology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. FAU - Paran, Sri AU - Paran S AD - Department of Paediatric Surgery, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. FAU - McAuliffe, Fionnuala M AU - McAuliffe FM AD - UCD Perinatal Research Centre, Obstetrics & Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland. FAU - Hogan, Andrew E AU - Hogan AE AD - National Children's Research Centre, Crumlin, Dublin 12, Ireland; Education and Research Centre and Conway Institute, St. Vincent's University Hospital, University College Dublin, Dublin 4, Ireland; Institute of Immunology, Department of Biology, Maynooth University, Maynooth, Co Kildare, Ireland. FAU - Doyle, Sarah L AU - Doyle SL AD - National Children's Research Centre, Crumlin, Dublin 12, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland. Electronic address: sarah.doyle@tcd.ie. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190323 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Cytokines) RN - 0 (Nucleic Acids) SB - IM MH - Adult MH - Body Mass Index MH - Child MH - Cytokines/*metabolism MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - Male MH - Mothers MH - Nucleic Acids/*metabolism MH - Overweight/*metabolism MH - Pediatric Obesity/*metabolism OTO - NOTNLM OT - Childhood obesity OT - Cytosolic nucleic acid OT - Maternal obesity OT - Proinflammatory cytokine EDAT- 2019/03/26 06:00 MHDA- 2020/08/07 06:00 CRDT- 2019/03/26 06:00 PHST- 2018/10/31 00:00 [received] PHST- 2019/03/19 00:00 [revised] PHST- 2019/03/20 00:00 [accepted] PHST- 2019/03/26 06:00 [pubmed] PHST- 2020/08/07 06:00 [medline] PHST- 2019/03/26 06:00 [entrez] AID - S1043-4666(19)30092-4 [pii] AID - 10.1016/j.cyto.2019.03.015 [doi] PST - ppublish SO - Cytokine. 2019 Jul;119:152-158. doi: 10.1016/j.cyto.2019.03.015. Epub 2019 Mar 23.