Modulation of mammalian immune effector cell functions by saliva of the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae)
Wasserman, Heather Anong
MetadataShow full item record
Immune responses to saliva of blood-feeding arthropods are important for both host and vector. Saliva contains factors that inhibit the host's hemostatic defenses, and these factors can be compromised by host immunity. In addition, transmission of many pathogens may be enhanced by vector saliva. This dissertation focuses on the effects of saliva of the yellow fever mosquito, Aedes aegypti, on mouse and human immune responses in vitro. A. aegypti saliva decreased proliferation and secretion of Th1/Th2 cytokines by mitogen- and antigen-stimulated mouse splenocytes and T-cells. Inhibition of lymphocyte function involved modulation of viable T-cells at low salivary gland extract (SGE) concentrations, and decreased viability at higher concentrations. Secretion of Th1/Th2 cytokines was inhibited, but Th1 cytokines were inhibited at lower SGE concentrations than the Th2. Dendritic cells remained viable at high SGE concentrations. A single salivary immunomodulatory component, 387kDa protein, was partially purified by HPLC. A. aegypti SGE inhibited several effector functions of stimulated mouse macrophages, including phagocytosis and MHC Class I/II expression. Macrophages incubated with SGE decreased secretion of pro-inflammatory cytokines, but low doses did not modulate IL-10. Inducible nitric oxide synthase was not inhibited. Neither cAMP nor PGE2-dependent signaling pathways were involved in immunomodulation. Saliva decreased proliferation of human PBMCs in a dose-dependent manner. Low doses of saliva stimulated CD4+ and CD8+ T-cell division, but higher doses were inhibitory. Secretion of IL-12 by saliva-treated PBMCs was stimulated, IFN-³ and TNF-± were not affected, and IL-2 was decreased. Secretion of GM-CSF, and the Th2 cytokines IL-5 and IL-13, was decreased. IL-4 secretion was not affected by saliva, and secretion of IL-10 was stimulated. IL-10 secretion from monocytes followed a similar pattern, IL-6 was stimulated, and TNF-± secretion was not affected. In neutrophils, both TNF-± and IL-6 were stimulated; IL-10 secretion was strongly inhibited. In dendritic cells, TNF-± and IL-10 secretion was inhibited by saliva. The results indicate that A. aegypti modulates a Th2 response in mice, and a more complex response with inflammatory and Th2 elements in humans. Characterization of these responses, and identification of the salivary components responsible, may be useful in the development of anti-arbovirus or transmission-blocking vaccines.