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Sex differences in innate immune function in neonates

Presented at the Neonatal Society 2018 Summer Meeting.

McGovern M1, Coyne S2, Flynn L2, Melo AM3, Moreno-Oliveria A3, Doherty DG3, Greene C4, Molloy EJ1,2,3,5,6

1 Trinity College, the University of Dublin
2 Coombe Women and Infants University Hospital Dublin
3 Trinity Translational Medicine Institute (TTMI), Trinity College Dublin
4 Royal College of Surgeons in Ireland, Dublin
5 Tallaght Hospital, Dublin
6 Neonatology, Our Lady’s Children’s Hospital, Crumlin, Dublin

Background: Neonatal sepsis remains a major cause of morbidity and mortality and research suggests that male neonates are at higher risk of sepsis than females and have poorer outcomes following episodes of sepsis. Females neonates are known to have a more robust immune response to infective stimuli than males (1) and steroid hormones such as estrogen are thought to affect the innate immune response (2). We hypothesise that males and female infants have differing innate immune responses and that these responses may be altered by the effect of steroid hormones. This study compared the expression of CD11b and TLR2 on the surface of granulocytes in male and female infants at term before and after endotoxin (LPS) and estrogen exposure.

Methods: Peripheral blood was taken from healthy neonates on the postnatal wards during routine phlebotomy (5 female, 7 male). Samples were treated with endotoxin (LPS; 10ng/mL) and 17-β estradiol (E2; 10-8M), alone and in combination. Samples were then stained with monoclonal antibodies specific for CD11b and TLR2 and analysed by flow cytometry. Granulocytes were identified based on light scattering properties and CD66b expression. Granulocyte activation was quantified by analysis of CD11b and TLR2 expression. Results were analysed using GraphPad Prism. Ethical approval was provided by the Coombe Women and Infants University Hospital and this project is funded by the National Children’s Research Centre, Dublin.

Results: No significant differences were noted in CD11b or TLR2 expression between male and female neonates at baseline. Male infants were found to be more responsive to endotoxin than females as they had a significant increase in CD11b following LPS exposure (p 0.0156), a difference not present in the female population (p >0.05). CD11b and TLR2 expression did not vary following E2 treatment.

Conclusion: CD11b and TLR2 expression did not differ between males and females at baseline. CD11b expression increased significantly following endotoxin exposure in males but not in females. Our findings support the theory that innate immune response differs by gender and this may have important implications for future research and should be considered in study design.

Corresponding author: elesean@hotmail.com

References
1. O’Driscoll DN, Greene CM, Molloy EJ. Expert review of clinical immunology. 2017;13(11):1061-71.
2. Giannoni E, Guignard L, Knaup Reymond M, et al. Infection and immunity. 2011;79(7):2690-8.

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