Aedes aegypti saliva impairs M1-associated proinflammatory phenotype without promoting or affecting M2 polarization of murine macrophages

Autor(es)

Barros, Michele S. ^[1] ; Lara, Priscila G. ^[1] ; Fonseca, Monique T. ^[2] ; Moretti, Eduardo H. ^[2] ; Filgueiras, Luciano R. ^[3] ; Martins, Joilson O. ^[4] ; Capurro, Margareth L. ^{[5, 6]} ; Steiner, Alexandre A. ^[2] ; Sa-Nunes, Anderson ^{[6, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Expt Immunol, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Sepsis Neurobiol, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Immunopharmacol, BR-05508000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Lab Immunoendocrinol, BR-05508000 Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Genetically Modified Mosquitoes, BR-05508000 Sao Paulo, SP - Brazil

^[6] Natl Council Sci & Technol Dev, Natl Inst Sci & Technol Mol Entomol, INCT EM CNPq, Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PARASITES & VECTORS; v. 12, MAY 16 2019.
• Citações Web of Science: 1

Resumo

BackgroundDuring the feeding process, the mouthparts of hematophagous mosquitoes break the skin barrier and probe the host tissue to find the blood. The saliva inoculated in this microenvironment modulates host hemostasis, inflammation and adaptive immune responses. However, the mechanisms involved in these biological activities remain poorly understood and few studies explored the potential roles of mosquito saliva on the individual cellular components of the immune system. Here, we report the immunomodulatory activities of Aedes aegypti salivary cocktail on murine peritoneal macrophages.ResultsThe salivary gland extract (SGE) of Ae. aegypti inhibited the production of nitric oxide and inflammatory cytokines such as interleukin-6 (IL-6) and IL-12, as well as the expression of inducible nitric oxide synthase and NF-B by murine macrophages stimulated by lipopolysaccharide (LPS) plus interferon- (IFN-). The spare respiratory capacity, the phagocytic and microbicidal activities of these macrophages were also reduced by Ae. aegypti SGE. These phenotypic changes are consistent with SGE suppressing the proinflammatory program of M1 macrophages. On the other hand, Ae. aegypti SGE did not influence M2-associated markers (urea production, arginase-1 and mannose receptor-1 expression), either in macrophages alternatively activated by IL-4 or in those classically activated by LPS plus IFN-. In addition, Ae. aegypti SGE did not display any cytokine-binding activity, nor did it affect macrophage viability, thus excluding supposed experimental artifacts.ConclusionsGiven the importance of macrophages in a number of biological processes, our findings help to enlighten how vector saliva modulates vertebrate host immunity. (AU)

• Processo FAPESP: 16/04921-1 - Tônus arterial no choque séptico: uma nova vertente para um velho problema.
• Beneficiário: Alexandre Alarcon Steiner
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/12467-0 - Efeito dos componentes salivares do mosquito Aedes aegypti na biologia de macrófagos e potenciais aplicações terapêuticas.
• Beneficiário: Michele Silva de Barros
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/22934-0 - Imunomodulação da encefalomielite autoimune experimental por proteínas salivares do mosquito Aedes aegypti.
• Beneficiário: Anderson de Sá Nunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/11540-7 - Investigando o papel da insulina na vigência da inflamação alérgica pulmonar em camundongos diabéticos e sadios
• Beneficiário: Joilson de Oliveira Martins
• Modalidade de apoio: Auxílio à Pesquisa - Regular