Anti-IL-4, Anti-IL-17, and Anti-IFN-Gamma Activity in the Saliva of Amblyomma sculptum Ticks

Int J Mol Sci. 2025 May 15;26(10):4734. doi: 10.3390/ijms26104734.

Abstract

The saliva of hematophagous arthropods, such as ticks and triatomines, contains bioactive ligands capable of modulating immune molecules, including cytokines. Cytokines play a critical role in immune regulation and have therapeutic relevance in inflammatory and immune-mediated diseases. Despite recent advances, identifying cytokine-binding molecules remains a significant challenge. Interferon-gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-17 (IL-17) are key cytokines involved in inflammation, adaptive immunity, and host defense. This study evaluated the ability of salivary components from Amblyomma sculptum and compared the results to the triatomine Rhodnius neglectus (used as control) to bind to IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α using ELISA assays with human cytokines. Saliva samples were tested at dilutions of 1:25, 1:50, and 1:100. Saliva from A. sculptum, which demonstrated significant anti-cytokine activity, was fractionated via HPLC to identify the active components. The results confirmed the inhibitory capacity of A. sculptum saliva on IFN-γ, IL-4, and IL-17, with inhibition rates ranging from 30% to 70%, depending on the cytokine and dilution. No inhibitory activity was observed against IL-2, IL-6, IL-10, or TNF-α. These findings underscore the immunomodulatory role of A. sculptum saliva during tick feeding and suggest its potential for the development of novel immunobiologics to treat inflammatory and immune-mediated diseases.

Keywords: Amblyomma sculptum; cytokine-binding proteins; immunomodulation; saliva; ticks.

MeSH terms

  • Amblyomma* / immunology
  • Amblyomma* / metabolism
  • Animals
  • Cytokines / metabolism
  • Humans
  • Interferon-gamma* / antagonists & inhibitors
  • Interferon-gamma* / immunology
  • Interferon-gamma* / metabolism
  • Interleukin-17* / antagonists & inhibitors
  • Interleukin-17* / immunology
  • Interleukin-17* / metabolism
  • Interleukin-4* / antagonists & inhibitors
  • Interleukin-4* / immunology
  • Interleukin-4* / metabolism
  • Saliva* / chemistry
  • Saliva* / immunology
  • Saliva* / metabolism

Substances

  • Interferon-gamma
  • Interleukin-4
  • Interleukin-17
  • Cytokines