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A study by Ludwig-Maximilians-Universitaet (LMU) in Munich researchers demonstrates that putatively immature dendritic cells found in young children are able to induce strong immune responses.
Dendritic cells are a vital component of the innate immune system, which represents the body’s first line of defense against infectious agents and tumor cells. Their job is to trigger the T-cell arm of the adaptive immune system, which confers long-lasting and specific protection against bacterial and viral infections.
Dendritic cells engulf and degrade proteins that indicate the presence of invasive pathogens. The resulting fragments (antigens) are displayed in their surfaces. T cells bearing the appropriate receptors are then activated to find and eliminate the pathogen.
However, new work published by a research team led by Professor Barbara Schraml in LMU’s Biomedical Center has shown – using the mouse as a model system – that this premise is in fact incorrect.
Although early dendritic cells differ in their characteristics from those of mice that are mature, they are nevertheless quite effective at triggering effective immune responses. The new findings indicate ways of boosting the effectiveness of vaccines for young children.
However, our experiments demonstrate that – in contrast to the conventional view – a particular subtype of dendritic cells named cDC2 cells is able to activate T-cells and express pro-inflammatory cytokines in young animals. In other words, very young mice can indeed trigger immune reactions.”
Barbara Schraml, Professor, Biomedical Center, Ludwig-Maximilians-Universitaet Muenchen (LMU)
With the help of fluorescent tags attached to specific proteins of interest, Schraml and her colleagues traced the roots and biological properties of dendritic cells in newborn and juvenile mice and compared them with those of mature animals.
These studies demonstrated that dendritic cells are derived from different source populations, based on the time of the animal believed. Those found in neonatal animals develop from precursor cells produced in the fetal liver.
Since the mice get older, these cells are progressively replaced by cells arising from myeloid precursors, a class of white blood cells that originates from the bone marrow.
Nevertheless, early cDC2 cells differ in some respects from those found in adult mice. For example, they reveal age-dependent differences in the sets of genes that they express. It turns out that these differences reflect the fact that the signaling molecules (‘cytokines’) to which dendritic cells respond to change as the mice get older.
“Among other things, the collection of receptors that recognize substances which are specific to pathogens changes with age,” states Schraml. “Another surprise for us was that ancient dendritic cells activate one specific subtype of T-cells more efficiently than others. Interestingly, this subtype has been implicated in the development of inflammatory responses.”
The results of the study represent a substantial contribution to our comprehension of the functions of dendritic cells, and they could have implications for medical immunology.
“Our data suggest that it may be possible to enhance the efficacy of vaccinations in childhood by, for instance, adapting the properties of the immunizing antigen into the specific capabilities of the juvenile dendritic cells,” says Schraml.
Ludwig-Maximilians-Universitaet Muenchen (LMU)
Papaioannou, N. E., et al. (2021) Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice. Nature Communications. doi.org/10.1038/s41467-020-20659-2.
