Insights into the molecular mechanisms of immune priming in An. gambiae mosquitoes.

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NIAID	MICROBIO-8

* FARE Award Winner

Authors

• J.L. Ramirez
• G. de Almeida Oliveira
• E. Calvo
• A.B. Barletta Ferreira
• C.N. Serhan
• J.M. Ribeiro
• C. Barillas-Mury

Abstract

An innate immune priming response is triggered when Plasmodium ookinetes invade the mosquito midgut and the microbiota comes in direct contact with injured cells. This is a long-lasting response that confers the mosquito enhanced ability to control subsequent Plasmodium infections. The immune priming response involves hemocyte differentiation, in particular an increase in the granulocyte population. A hemocyte differentiation factor (HDF) is released into the hemolymph and transfer of cell-free hemolymph from challenged mosquitoes can induce hemocyte differentiation and enhanced immunity in recipient naïve mosquitoes. Here, we have characterized the biochemical nature of HDF. We found that it consists of a bioactive lipid that is transported in the hemolymph by a lipocalin (ApoD-like) carrier protein. RNAi-based silencing of this Apo-D-like abolished the release of HDF activity in the hemolymph extract, indicating that it is a critical component of the immune priming response. LC/MS/MS analysis showed that the HDF lipid component is an eicosanoid in nature. Injection of synthetic eicosanoid analogs recapitulates the phenotype observed in Plasmodium-infected mosquitoes as well as those observed when transferring cell-free hemolymph from challenged to naïve mosquitoes. Currently, we are further characterizing the identity of the bioactive lipids that mediate innate immune memory in An. gambiae mosquitoes.

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