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Published on: October 25, 2018
Maternal allergy influences p38-mitogen-activated protein kinase activity upon microbial challenge in CD14+ monocytes
S Saghafian-Hedengren1, U Holmlund, P Amoudruz
1Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. shanie@imun.su.se
Insights
Infants born to mothers with allergies show a weaker immune response to bacteria. This reduced monocyte responsiveness persists for at least two years, impacting early childhood immunity.
Area of Science:
- Immunology
- Allergy Research
- Pediatric Health
Background:
- Allergic disease development is influenced by genetic and environmental factors.
- Cord blood mononuclear cells (CBMCs) from infants of allergic mothers exhibit altered cytokine profiles.
- Immune impairments in early childhood may stem from maternal allergy.
Purpose of the Study:
- To investigate antimicrobial responses in children at birth and two years of age.
- To analyze p38-mitogen-activated protein kinase (MAPK) activity in CD14(+) monocytes.
- To quantify Interleukin-6 (IL-6) release from mononuclear cells in relation to maternal allergy.
Main Methods:
- Paired CBMC and peripheral blood mononuclear cell (PBMC) samples were collected at birth and two years.
- In vitro stimulation with lipopolysaccharide (LPS) or peptidoglycan.
- Flow cytometry for p38-MAPK activation; ELISA for IL-6, soluble IL-6 receptor, and soluble glycoprotein130.
Main Results:
- Newborns with allergic mothers showed a trend towards lower IL-6 response to LPS.
- Two-year-olds with allergic mothers had significantly reduced IL-6 release upon peptidoglycan stimulation.
- Infants of allergic mothers displayed reduced p38-MAPK phosphorylation in monocytes after bacterial challenge.
Conclusions:
- Monocytes from children with allergic mothers are less responsive to bacterial stimuli.
- This impaired antimicrobial response is linked to maternal allergy, not IgE sensitization.
- Immune hypo-responsiveness persists through the first two years of infancy.
Background:
The development of allergic diseases is dependent on genetic and environmental factors. It has been shown previously that cord blood mononuclear cells (CBMCs) from infants with parental allergy have altered cytokine profiles upon bacterial encounter; it might be possible that such impairment persists during the early years of childhood.
Objective:
The aim of this study was to investigate anti-microbial responses with regard to p38-mitogen-activated protein kinase (MAPK) activity in CD14(+) monocytes and IL-6 release from mononuclear cells in the same group of children at birth and at 2 years of age. Methods Paired samples of CBMCs and peripheral blood mononuclear cells (PBMCs) were stimulated with either lipopolysaccharide (LPS) or peptidoglycan in vitro. CD14(+) monocytes were analysed for p38-MAPK activity by flow cytometry, and soluble IL-6 receptor, soluble glycoprotein130 and IL-6 release from PBMC cultures were quantified by ELISA.
Results:
CBMCs from newborns with allergic mothers tended to have a lower IL-6 response following an LPS (P=0.09) challenge compared with the group without maternal allergy while p38-MAPK activation levels did not differ between the groups. PBMCs from 2-year-olds with allergic mothers released significantly less (P<0.05) IL-6 upon peptidoglycan stimuli compared with age-matched infants with non-allergic mothers. Infants with allergic mothers displayed markedly reduced CD14(+) monocyte p38-MAPK phosphorylation after LPS (P<0.05) and peptidoglycan (P<0.01) challenge. This altered anti-microbial response was attributed to maternal allergy rather than to being IgE-sensitized at 2 years of age.
Conclusion:
Monocytes from children with allergic mothers are less responsive to bacterial challenge than monocytes from children with non-allergic mothers, and this impairment persists during the first 2 years of infancy.
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