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Cord blood monocyte subsets are similar to adult and show potent peptidoglycan-stimulated cytokine responses
Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
2011 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 133, no 1, 41-50 p.Article in journal (Refereed) Published
Abstract [en]

P>Human monocytes can be divided into two major subpopulations, CD14++ CD16- and CD14+ CD16+ cells, which are suggested to play different roles in antimicrobial responses. In neonates, characteristics and functional responses of monocyte subsets have not previously been explored, and might contribute to the qualitative difference between neonatal and adult cytokine profiles. We report that at baseline, monocyte subsets in cord blood and adult peripheral blood are present in similar frequencies, and show similar expression of CD11c, CD80/CD86, CD163 and HLA-DR. In response to the bacterial ligand peptidoglycan, cord blood monocytes had high inherent capacity for production of the early-response cytokines with levels of tumour necrosis factor and interleukin-12p70 exceeding adult levels, and also a higher phosphorylation of p38-mitogen-activated protein kinase. The CD14+ CD16+ cells expressed more interleukin-12p70 than CD14++ CD16- cells and were present in a higher frequency in peptidoglycan-stimulated cord blood mononuclear cell cultures. Together, the behaviour of cord blood CD14+ CD16+ cells following peptidoglycan stimulation might indicate a qualitative difference between the neonatal antimicrobial response and that of the adult. In addition we found that serum factors in cord blood and adult sera affected cytokine production similarly, with the exception of tumour necrosis factor, regardless of the source of serum or cells. Overall, our data provide new insights into monocyte heterogeneity in cord blood and monocyte subset responses to a bacterial ligand at birth.

Place, publisher, year, edition, pages
2011. Vol. 133, no 1, 41-50 p.
Keyword [en]
CD14++CD16-cells, CD14+CD16+cells, interleukin-12p70, neonatal immunity, tumour necrosis factor
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-68518DOI: 10.1111/j.1365-2567.2011.03407.xISI: 000289160000005OAI: oai:DiVA.org:su-68518DiVA: diva2:473423
Funder
Swedish Research Council, K2010-57X-15160-07-3
Note

4

Available from: 2012-01-05 Created: 2012-01-04 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Immune maturation in early childhood and the influence of herpesvirus infections
Open this publication in new window or tab >>Immune maturation in early childhood and the influence of herpesvirus infections
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The quality of immune responses develops from birth into adulthood and in the context of the host microbial environment. The aim of this work was to study immune maturation during childhood, and how this process can be affected by the common herpesviruses; Epstein-Barr virus (EBV) and cytomegalovirus (CMV).

In paper I we studied monocytes, an important cell type for immunity in the newborn. We showed that the neonatal monocyte subsets exist in similar frequencies as adult subsets, and have a potent capacity for pro-inflammatory cytokine production. In paper II, III and IV we studied the effects of EBV and CMV infections on immune cell function in children. In paper II we found that monocyte-induced NK-cell production of IFN-γ, and plasma IFN-γ levels, were decreased in 2-year old EBV- and/or CMV-seropositive children and mostly so in co-infected children. In paper III we found that in 5-year old children, EBV and CMV co-infection was associated with the highest levels of differentiated NKG2C+ NK cells. CMV+ children had higher plasma IFN-γ and IL-15 levels and higher NK-cell cytotoxic capacity. In vitro PBMC systems showed elevated frequencies of NKG2C+ NK cells in the presence of EBV-infected cells. In paper IV we showed that a child’s age and subsequent capacity for anti-viral cytokine production affects in vitro EBV infection in terms of B-cell proliferation and B-cell acquisition of memory phenotype. PBMC from CMV+ children had lower EBV-induced accumulation of switched memory B cells, which was connected to high prevalence of CD57+CD8+ T cells and IFN-γ production.

Taken together, this thesis work shows that monocyte subsets at birth can give potent functional responses and that latency with EBV and CMV has a significant effect on the differentiation process and functional capacity of anti-viral effector cells during childhood. This in turn could affect responses to related or unrelated infections or even to non-invasive antigens such as allergens.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2013. 91 p.
Keyword
Immune differentiation, monocytes, NK cells, B cells, T cells, Epstein-Barr virus; EBV, cytomegalovirus; CMV, IFN-γ
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-93034 (URN)978-91-7447-745-0 (ISBN)
Public defence
2013-10-11, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2013-09-19 Created: 2013-08-29 Last updated: 2013-09-17Bibliographically approved

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