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

Parasites & Vectors

Michele S. Barros¹  Priscila G. Lara¹  Anderson Sá-Nunes²  Margareth L. Capurro³  Joilson O. Martins⁴  Luciano R. Filgueiras⁵  Monique T. Fonseca⁶  Eduardo H. Moretti⁶  Alexandre A. Steiner⁶ 

[1] 0000 0004 1937 0722, grid.11899.38, Laboratory of Experimental Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil;0000 0004 1937 0722, grid.11899.38, Laboratory of Experimental Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil;0000 0001 2189 2026, grid.450640.3, National Institute of Science and Technology on Molecular Entomology, National Council for Scientific and Technological Development (INCT-EM/CNPq), Rio de Janeiro, RJ, Brazil;0000 0004 1937 0722, grid.11899.38, Laboratory of Genetically Modified Mosquitoes, Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil;0000 0001 2189 2026, grid.450640.3, National Institute of Science and Technology on Molecular Entomology, National Council for Scientific and Technological Development (INCT-EM/CNPq), Rio de Janeiro, RJ, Brazil;0000 0004 1937 0722, grid.11899.38, Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil;0000 0004 1937 0722, grid.11899.38, Laboratory of Immunopharmacology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil;0000 0004 1937 0722, grid.11899.38, Laboratory of Sepsis Neurobiology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil;

关键词: Aedes aegypti;    Saliva;    Macrophages;    Inflammation;    M1/M2 polarization;    microbicidal activity;   

DOI  :  10.1186/s13071-019-3487-7

来源: publisher

【 摘 要 】

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-κB by murine macrophages stimulated by lipopolysaccharide (LPS) plus interferon-γ (IFN-γ). 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-γ. 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.

【 授权许可】

CC BY