David N O'Driscoll1,2,3, Chiara De Santi4, Paul J McKiernan2, Victoria McEneaney3, Eleanor J Molloy1,2,3,5,6, Catherine M Greene4. 1. Neonatology, National Maternity Hospital, Dublin, Ireland. 2. Respiratory Research, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. 3. Paediatrics, Academic Centre, Tallaght Hospital, Trinity College, The University of Dublin, Dublin, Ireland. 4. Clinical Microbiology, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. 5. Neonatology, Coombe Women and Infants' University Hospital, Dublin, Ireland. 6. Neonatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
Abstract
BACKGROUND: Male neonates display poorer disease prognosis and outcomes compared with females. Immune genes which exhibit higher expression in umbilical cord blood (UCB) of females may contribute to the female immune advantage during infection and inflammation. The aim of this study was to quantify expression of Toll-like receptor (TLR) 4 signaling genes encoded on the X-chromosome in UCB from term female vs. male neonates. METHODS: UCB samples were collected from term neonates (n = 26) born by elective Caesarean section and whole blood was collected from adults (n = 20). Leukocyte RNA was isolated and used in quantitative PCR reactions for IκB kinase γ (IKKγ), Bruton's tyrosine kinase (BTK), and IL-1 receptor associated kinase (IRAK)1. IRAK1 protein was analyzed by Western blot and confocal microscopy. RESULTS: In neonates there was no significant difference in the relative expression of IKKγ or BTK mRNA between genders. IRAK1 gene and protein expression was significantly higher in female vs. male UCB, with increased cytosolic IRAK1 expression also evident in female UCB mononuclear cells. Adults had higher expression of all three genes compared with neonates. CONCLUSION: Increased expression of IRAK1 could be responsible, in part, for sex-specific responses to infection and subsequent immune advantage in female neonates.
BACKGROUND: Male neonates display poorer disease prognosis and outcomes compared with females. Immune genes which exhibit higher expression in umbilical cord blood (UCB) of females may contribute to the female immune advantage during infection and inflammation. The aim of this study was to quantify expression of Toll-like receptor (TLR) 4 signaling genes encoded on the X-chromosome in UCB from term female vs. male neonates. METHODS: UCB samples were collected from term neonates (n = 26) born by elective Caesarean section and whole blood was collected from adults (n = 20). Leukocyte RNA was isolated and used in quantitative PCR reactions for IκB kinase γ (IKKγ), Bruton's tyrosine kinase (BTK), and IL-1 receptor associated kinase (IRAK)1. IRAK1 protein was analyzed by Western blot and confocal microscopy. RESULTS: In neonates there was no significant difference in the relative expression of IKKγ or BTK mRNA between genders. IRAK1 gene and protein expression was significantly higher in female vs. male UCB, with increased cytosolic IRAK1 expression also evident in female UCB mononuclear cells. Adults had higher expression of all three genes compared with neonates. CONCLUSION: Increased expression of IRAK1 could be responsible, in part, for sex-specific responses to infection and subsequent immune advantage in female neonates.
Authors: Mustapha Chamekh; Maud Deny; Marta Romano; Nicolas Lefèvre; Francis Corazza; Jean Duchateau; Georges Casimir Journal: Front Immunol Date: 2017-12-13 Impact factor: 7.561
Authors: Sarah Pyfrom; Bam Paneru; James J Knox; Michael P Cancro; Sylvia Posso; Jane H Buckner; Montserrat C Anguera Journal: Proc Natl Acad Sci U S A Date: 2021-06-15 Impact factor: 11.205