Dataset Information

Neonatal immune response to rhinovirus A16 has diminished dendritic cell function and increased B cell activation.

ABSTRACT:

Background

Rhinovirus infections during infancy account for the majority of respiratory illness health care utilization and are an associated risk factor for subsequent development of allergic asthma. Neonatal type I interferon production is diminished compared to adults after stimulation with TLR agonists. However, broad profiling of immune cell responses to infectious rhinovirus has not been undertaken and we hypothesized that additional immune differences can be identified in neonates. In this study, we undertook a comparative analysis of neonatal and adult blood immune cell responses after in vitro incubation with infectious RV-A16 for 6 and 24 hours.

Methods

Intracellular proinflammatory and type I interferon cytokines along with expression of surface co-stimulatory and maturation markers were measured using multi-parameter flow cytometry.

Results

Both circulating myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) frequency were lower in cord blood. Qualitative and quantitative plasmacytoid dendritic cell IFN-alpha + TNF- alpha responses to rhinovirus were significantly lower in cord pDCs. In cord blood samples, the majority of responsive pDCs were single-positive TNF-alpha producing cells, whereas in adult samples rhinovirus increased double-positive TNF-alpha+IFN-alpha+ pDCs. Rhinovirus upregulated activation and maturation markers on monocytes, mDCs, pDCs, and B cells, but CD40+CD86+ monocytes, mDCs, and pDCs cells were significantly higher in adult samples compared to cord samples. Surprisingly, rhinovirus increased CD40+CD86+ B cells to a significantly greater extent in cord samples compared to adults.

Conclusions

These findings define a number of cell-specific differences in neonatal responses to rhinovirus. This differential age-related immune response to RV may have implications for the immune correlates of protection to viral respiratory illness burden and determination of potential biomarkers for asthma risk.

SUBMITTER: Barlow-Anacker A

PROVIDER: S-EPMC5646756 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Neonatal immune response to rhinovirus A16 has diminished dendritic cell function and increased B cell activation.

Barlow-Anacker Amanda A Bochkov Yury Y Gern James J Seroogy Christine M CM

PloS one 20171018 10

<h4>Background</h4>Rhinovirus infections during infancy account for the majority of respiratory illness health care utilization and are an associated risk factor for subsequent development of allergic asthma. Neonatal type I interferon production is diminished compared to adults after stimulation with TLR agonists. However, broad profiling of immune cell responses to infectious rhinovirus has not been undertaken and we hypothesized that additional immune differences can be identified in neonates ...[more]

PMID: 29045416

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Project description:Does medroxyprogesterone acetate (MPA) impair human dendritic cell (DC) activation and function?In vitro MPA treatment suppressed expression of CD40 and CD80 by human primary DCs responding to Toll-like receptor 3 (TLR3) agonist stimulation (i.e. DC activation). Moreover, this MPA-mediated decrease in CD40 expression impaired DC capacity to stimulate T cell proliferation (i.e. DC function).MPA is the active molecule in Depo-Provera(®) (DMPA), a commonly used injectable hormonal contraceptive (HC). Although DMPA treatment of mice prior to viral mucosal tissue infection impaired the capacity of DCs to up-regulate CD40 and CD80 and prime virus-specific T cell proliferation, neither DC activation marker expression nor the ability of DCs to promote T cell proliferation were affected by in vitro progesterone treatment of human DCs generated from peripheral blood monocytes.This cross-sectional study examined MPA-mediated effects on the activation and function of human primary untouched peripheral blood DCs.Human DCs isolated from peripheral blood mononuclear cells by negative immunomagnetic selection were incubated for 24 h with various concentrations of MPA. After an additional 24 h incubation with the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C), flow cytometry was used to evaluate DC phenotype (i.e. expression of CD40, CD80, CD86, and HLA-DR). In separate experiments, primary untouched human DCs were sequentially MPA-treated, poly I:C-activated, and incubated for 7 days with fluorescently labeled naïve allogeneic T cells. Flow cytometry was then used to quantify allogeneic T cell proliferation.Several pharmacologically relevant concentrations of MPA dramatically reduced CD40 and CD80 expression in human primary DCs responding to the immunostimulant poly I:C. In addition, MPA-treated DCs displayed a reduced capacity to promote allogeneic CD4(+) and CD8(+) T cell proliferation. In other DC: T cell co-cultures, the addition of antibody blocking the CD40-CD154 (CD40L) interaction mirrored the decreased T cell proliferation produced by MPA treatment, while addition of recombinant soluble CD154 restored the capacity of MPA-treated DCs to induce T cell proliferation to levels produced by non-MPA-treated controls.While our results newly reveal that pharmacologically relevant MPA concentrations suppress human DC function in vitro, additional research is needed to learn if DMPA similarly inhibits DC maturation and function in the human female genital tract.Identification of a mechanism by which MPA impairs human DC activation and function increases the biological plausibility for the relationships currently suspected between DMPA use and enhanced susceptibility to genital tract infection.Funding provided by the NIH (grant R01HD072663) and The Ohio State University College of Medicine. The authors have no con?icts of interest to declare.

Dataset Information

Neonatal immune response to rhinovirus A16 has diminished dendritic cell function and increased B cell activation.

Background

Methods

Results

Conclusions

Publications

Neonatal immune response to rhinovirus A16 has diminished dendritic cell function and increased B cell activation.

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