Mosquito saliva alone--even in the absence of any pathogens--contains hundreds of proteins. Now, researchers reporting in PLOS Neglected Tropical Diseases have discovered that the interaction of these proteins with the human immune system causes an immune response that can be detected for days after a mosquito bite.
Around the globe, 750,000 people a year die of mosquito-transmitted diseases, including malaria, dengue, West Nile, Zika, and chikungunya fever. Previous studies have shown that properties of a mosquito bite--including mosquito saliva--exacerbate some of these diseases; in mice, infections caused by a mosquito bite are often more severe than those caused by needle injection of the parasite.
In their new work, Rebecca Rico-Hesse, of Baylor College of Medicine, USA, and colleagues studied the effect of mosquito bites on human immune cells in mice engrafted with human hematopoietic stem cells--leading the animals to have components of a human immune system. They studied small changes in the levels and functions of these immune cells after each mouse was bitten by four mosquitoes on their footpads.
After getting bitten by mosquitoes uninfected with any pathogen, the humanized mice showed multiple types of human immune responses, with altered Th1 and Th2 T helper cells and an increase in the levels of cytokines. At various points during the immune responses, there were also increases to levels of natural killer T cells, natural killer cells, CD8+ T cells, mononocytes, and macrophages. Overall, evidence of the immune responses lasted up to 7 days post-bite and were seen in multiple tissue types, including the blood, skin and bone marrow.
"Understanding how mosquito saliva interacts with the human immune system not only helps us understand mechanisms of disease pathogenesis but also could provide possibilities for treatments," the researchers say.
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Citation: Vogt MB, Lahon A, Arya RP, Kneubehl AR, Spencer Clinton JL, et al. (2018) Mosquito saliva alone has profound effects on the human immune system. PLOS Neglected Tropical Diseases 12(5): e0006439. https:/
Funding: This work was supported by the National Institutes of Health grants to RR-H (grant numbers R01 AI098715, R01 AI099483). This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (P30 AI036211, P30 CA125123, and S10 RR024574) and the expert assistance of Joel M. Sederstrom. Additionally, this project was supported by the Antibody Based Proteomics Core at Baylor College of Medicine with funding from the NIH (P30 NC1-CA125123) and CPRIT (RP120092) with the expert assistance of Shixia Huang. Stereophotography was done with the support of the Optical Imaging & Vital Microscopy Core, Mary E. Dickinson, PhD, Academic Director,at Baylor College of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.