Abstract
BackgroundSex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs).ResultsIn this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-α production following R-848 challenge.ConclusionsAndrogen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy.
Highlights
Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells
The effect of sex on Plasmacytoid dendritic cell (pDC) may have a cost of higher rates of systemic lupus erythematosus (SLE) and autoimmune diseases later in adult females compared to adult males [12,13]
We found that the percentage of IFN-α + pDCs (Figure 1b), but not tumor necrosis factor-α (TNF-α) + pDCs (Figure 1c), was significantly higher in female infants compared to male infants following 1 μM R-848 stimulation
Summary
Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs). Results: In this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Sex differences in adult pDC IFN-α production have been previously described, with production being higher in females than males [8,9]. The reported effects of female sex hormones on TLR7-mediated pDC IFN-α production have been varied [8,9,10]. We found that during the “mini-puberty” period female infant pDCs have higher pDC IFN-α production than male infants in response to 1 μM R-848 stimulation. Androgen signaling downregulated R-848 stimulated pDC IFN-α production This sex effect on pDC IFN-α production may play a role in the female survival benefit seen during early infancy. We describe a novel effect of male sex hormones on TLR7-mediated pDC IFN-α production
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