Effects of Aedes aegypti salivary components on dendritic cell and lymphocyte biology

Abstract

BackgroundSaliva is a key element of interaction between hematophagous mosquitoes and their vertebrate hosts. In addition to allowing a successful blood meal by neutralizing or delaying hemostatic responses, the salivary cocktail is also able to modulate the effector mechanisms of host immune responses facilitating, in turn, the transmission of several types of microorganisms. Understanding how the mosquito uses its salivary components to circumvent host immunity might help to clarify the mechanisms of transmission of such pathogens and disease establishment.MethodsFlow cytometry was used to evaluate if increasing concentrations of A. aegypti salivary gland extract (SGE) affects bone marrow-derived DC differentiation and maturation. Lymphocyte proliferation in the presence of SGE was estimated by a colorimetric assay. Western blot and Annexin V staining assays were used to assess apoptosis in these cells. Naïve and memory cells from mosquito-bite exposed mice or OVA-immunized mice and their respective controls were analyzed by flow cytometry.ResultsConcentration-response curves were employed to evaluate A. aegypti SGE effects on DC and lymphocyte biology. DCs differentiation from bone marrow precursors, their maturation and function were not directly affected by A. aegypti SGE (concentrations ranging from 2.5 to 40 μg/mL). On the other hand, lymphocytes were very sensitive to the salivary components and died in the presence of A. aegypti SGE, even at concentrations as low as 0.1 μg/mL. In addition, A. aegypti SGE was shown to induce apoptosis in all lymphocyte populations evaluated (CD4+ and CD8+ T cells, and B cells) through a mechanism involving caspase-3 and caspase-8, but not Bim. By using different approaches to generate memory cells, we were able to verify that these cells are resistant to SGE effects.ConclusionOur results show that lymphocytes, and not DCs, are the primary target of A. aegypti salivary components. In the presence of A. aegypti SGE, naïve lymphocyte populations die by apoptosis in a caspase-3- and caspase-8-dependent pathway, while memory cells are selectively more resistant to its effects. The present work contributes to elucidate the activities of A. aegypti salivary molecules on the antigen presenting cell-lymphocyte axis and in the biology of these cells.

Effect of the saliva from different triatomine species on the biology and immunity of TLR-4 ligand and Trypanosoma cruzi-stimulated dendritic cells

“…Although it seems a standard effect for blood-sucking arthropods, saliva’s ability to inhibit the differentiation of DCs is not common to all of them, e.g. Aedes aegypti mosquito saliva is not able to inhibit the differentiation of these cells [29]. …”

Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

“…Aedes aegypti mosquitoes (male and female) were bred in an insectary at the Department of Parasitology, ICB/USP, Brazil, where they were fed and mated as previously described . Five‐ to eight‐day‐old female adult mosquitoes were used for the experimental mice sensitization and SGE preparation as described …”

Smuggling across the Border: How Arthropod-Borne Pathogens Evade and Exploit the Host Defense System of the Skin

“…Parasitemia was higher and cerebral malaria developed more frequently (Depinay et al, 2006;Schneider et al, 2011;Mauduit et al, 2012). The saliva of Aedes aegyti also exhibits immunomodulatory properties by inducing lymphocyte but not DC apoptosis in a caspase 3-and 8-dependent pathway (Bizzarro et al, 2013).…”