AeMOPE-1, a Novel Salivary Peptide From Aedes aegypti, Selectively Modulates Activation of Murine Macrophages and Ameliorates Experimental Colitis

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Lara, Priscila G. ; Esteves, Eliane ; Sales-Campos, Helioswilton ; Assis, Josiane B. ; Henrique, Maressa O. ; Barros, Michele S. ; Neto, Leila S. ; Silva, Pedro, I ; Martins, Joilson O. ; Cardoso, Cristina R. B. ; Ribeiro, Jose M. C. ; Sa-Nunes, Anderson

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 12, p. 15-pg., 2021-07-19.

Resumo

The sialotranscriptomes of Aedes aegypti revealed a transcript overexpressed in female salivary glands that codes a mature 7.8 kDa peptide. The peptide, specific to the Aedes genus, has a unique sequence, presents a putative secretory nature and its function is unknown. Here, we confirmed that the peptide is highly expressed in the salivary glands of female mosquitoes when compared to the salivary glands of males, and its secretion in mosquito saliva is able to sensitize the vertebrate host by inducing the production of specific antibodies. The synthetic version of the peptide downmodulated nitric oxide production by activated peritoneal murine macrophages. The fractionation of a Ae. aegypti salivary preparation revealed that the fractions containing the naturally secreted peptide reproduced the nitric oxide downmodulation. The synthetic peptide also selectively interfered with cytokine production by murine macrophages, inhibiting the production of IL-6, IL-12p40 and CCL2 without affecting TNF-alpha or IL-10 production. Likewise, intracellular proteins associated with macrophage activation were also distinctively modulated: while iNOS and NF-kappa B p65 expression were diminished, I kappa B alpha and p38 MAPK expression did not change in the presence of the peptide. The anti-inflammatory properties of the synthetic peptide were tested in vivo on a dextran sulfate sodium-induced colitis model. The therapeutic administration of the Ae. aegypti peptide reduced the leukocytosis, macrophage activity and nitric oxide levels in the gut, as well as the expression of cytokines associated with the disease, resulting in amelioration of its clinical signs. Given its biological properties in vitro and in vivo, the molecule was termed Aedes-specific MOdulatory PEptide (AeMOPE-1). Thus, AeMOPE-1 is a novel mosquito-derived immunobiologic with potential to treat immune-mediated disorders. (AU)

• Processo FAPESP: 20/03175-0 - Investigando mecanismos que ligam angiotensinas à Obesidade e Diabetes
• Beneficiário: Joilson de Oliveira Martins
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/00740-4 - Peptídeos salivares de Aedes aegypti
• Beneficiário: Priscila Guirão Lara
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/09892-6 - Imunoma funcional da saliva de Aedes aegypti
• Beneficiário: Anderson de Sá Nunes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• 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: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs