ArticleFrontiers in immunology2025
Estradiol enhances B cell humoral immune responses against genital herpes simplex virus type 2 in mice through an IL-17 dependant pathway.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Sex differences in immune modulation: implications for infection, inflammation, and nutritional supplementation.Biology of sex differences · 2026Review
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8 authors.
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Abstract
Introduction: Estradiol has been shown to enhance anti-viral immunity and protect against HSV-2 infection. Previously, we reported that intranasal immunization with attenuated HSV-2 (TK-) in the presence of estradiol (E2) showed enhanced Th17 responses that led to increased anti-viral Th1 immunity in HSV-2 post-challenge. Whether enhanced Th17 cells also lead to improved B cell antibody responses against HSV-2 challenge in immunized mice in the presence of E2 was not examined and is the focus of the current study. Methods: Ovariectomized (OVX) C57BL/6 or IL-17 knockout (IL-17-/-) mice were implanted with 17β-estradiol (E2) or placebo pellets subcutaneously. Two weeks later, mice were immunized intranasally with a single dose of 10 Results: E2-treated WT OVX immunized mice after intravaginal HSV-2 challenge showed significantly increased HSV-2-specific IgG2b and IgG2c antibodies in serum and vaginal secretions compared to placebo mice and enhanced B220-CD138+ IgG2c+ plasma cells within the nasal mucosa and vaginal tract 6-weeks after immunization. Furthermore, E2 treatment enhanced the subsets of CD19+ IgD- memory B cells 4-weeks post immunization within the iLN and spleen. Notably, E2-induced increased B cell antibody responses conferred greater protection from HSV-2 challenge compared to placebo mice as evidenced by 2-3 logs decreased viral titers in the vaginal tract and 20% mice with genital pathology compared to 80% in placebo group, indicating better protection in E2-treated mice. Importantly, E2-mediated enhanced plasma and B cell antibody responses observed in WT mice were abrogated in IL-17-/- mice that led to 2-3 logs higher viral titers that were equivalent in WT placebo- and IL-17-/- mice and no difference in protection. Conclusion: This study provides novel evidence that part of the E2-induced enhanced anti-viral response is mediated by increased B cell antibody responses that requires IL-17. Thus, E2 could be exploited in developing an effective mucosal vaccine driving B cells through intranasal immunization to elicit stronger HSV-2-specific antibody responses in the female genital tract.
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