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

Author(s):Show less -

Bizzarro, Bruna ^[1] ; Barros, Michele S. ^[1] ; Maciel, Ceres ^[1] ; Gueroni, Daniele I. ^[1] ; Lino, Ciro N. ^[1] ; Campopiano, Julia ^[2] ; Kotsyfakis, Michalis ^[3] ; Amarante-Mendes, Gustavo P. ^{[2, 4]} ; Calvo, Eric ^[5] ; Capurro, Margareth L. ^{[6, 7]} ; Sa-Nunes, Anderson ^{[7, 1]}

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Expt, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Biol Celular & Mol, BR-05508900 Sao Paulo - Brazil

^[3] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Lab Genom & Prote Dis Vectors, CR-37005 Ceske Budejovice - Czech Republic

^[4] Inst Nacl Ciencia & Tecnol, Inst Invest Imunol, Sao Paulo - Brazil

^[5] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 - USA

^[6] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Lab Mosquitos Geneticamente Modificados, BR-05508900 Sao Paulo - Brazil

^[7] Conselho Nacl Desenvolvimento Cient & Tecnol INCT, Inst Nacl Ciencia & Tecnol Entomol Mol, Rio De Janeiro - Brazil

• Document type: Journal article
• Source: PARASITES & VECTORS; v. 6, NOV 15 2013.
• Web of Science Citations: 21

Abstract

Background: Saliva 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. Methods: Flow 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. Naive and memory cells from mosquito-bite exposed mice or OVA-immunized mice and their respective controls were analyzed by flow cytometry. Results: Concentration-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 mu g/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 mu g/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. Conclusion: Our results show that lymphocytes, and not DCs, are the primary target of A. aegypti salivary components. In the presence of A. aegypti SGE, naive 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. (AU)

• FAPESP's process: 09/53637-0 - Anopheles-Plasmodium interaction: a multidisciplinary approach
• Grantee: Margareth de Lara Capurro-Guimarães
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 11/15569-3 - Characterization of the biological activity of Aedes aegypti salivary serpin AET-7393
• Grantee: Ciro Novaes Rosa Lino
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 09/12247-5 - Effect of Aedes aegypti saliva on the differentiation, maturation and function of dendritic cells
• Grantee: Bruna Bizzarro
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 09/09892-6 - Functional immunome of Aedes aegypti saliva
• Grantee: Anderson de Sá Nunes
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 10/18216-1 - Role of host immunity on biological fitness of Aedes aegypti mosquito vector
• Grantee: Ceres Maciel de Miranda
• Support type: Scholarships in Brazil - Post-Doctorate