Emerging role of lipid droplets in Aedes aegypti immune response against bacteria and Dengue virus

Abstract

In mammals, lipid droplets (LDs) are ubiquitous organelles that modulate immune and inflammatory responses through the production of lipid mediators. In insects, it is unknown whether LDs play any role during the development of immune responses. We show that Aedes aegypti Aag2 cells – an immune responsive cell lineage – accumulates LDs when challenged with Enterobacter cloacae, Sindbis, and Dengue viruses. Microarray analysis of Aag2 challenged with E.cloacae or infected with Dengue virus revealed high transcripts levels of genes associated with lipid storage and LDs biogenesis, correlating with the increased LDs numbers in those conditions. Similarly, in mosquitoes, LDs accumulate in midgut cells in response to Serratia marcescens and Sindbis virus or when the native microbiota proliferates, following a blood meal. Also, constitutive activation of Toll and IMD pathways by knocking-down their respective negative modulators (Cactus and Caspar) increases LDs numbers in the midgut. Our results show for the first time an infection-induced LDs accumulation in response to both bacterial and viral infections in Ae. Aegypti, and we propose a role for LDs in mosquito immunity. These findings open new venues for further studies in insect immune responses associated with lipid metabolism.

A mosquito juvenile hormone binding protein (mJHBP) regulates the activation of innate immune defenses and hemocyte development

“…At 72 h post-infection mortality remained very low, but bacterial levels in the KO strain dropped significantly ( Fig 3A) and remained higher than those of WT mosquitoes, showing that induction of the immune response eventually occurred but was delayed. The same trend was observed when mortality was measured after infection with a highly pathogenic strain of Serratia marcescens [14]. At 24 h post infection, 35% of KO mosquitoes survived, compared with over 80% of WT insects (Fig 3B).…”

“…Serratia marscescens [14] and ampicillin resistant (Amp R ) Escherichia coli were used for bacterial challenge. An Amp R E. coli strain was constructed by transformation with the plasmid pUC19.…”

Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila

“…Interestingly, lipid droplets have been shown to accumulate in neutrophils and macrophages during infection in mammals (50). Moreover, the constitutive activation of Toll and Imd pathways in Aedes mosquitoes leads to the accumulation of lipid droplets in the midgut (40,49). Therefore, our present findings indicate that the induction of Toll and Imd signaling in flies with inactivated tep genes could be linked to changes in the numbers of lipid droplets in the context of Photorhabdus infection.…”

“…They are abundantly present in fat-storing tissues, such as insect fat body cells. Lipid droplets perform immune activities in mammals, mosquitoes, and Drosophila (40,49,50). Interestingly, lipid droplets have been shown to accumulate in neutrophils and macrophages during infection in mammals (50).…”

Catalase protects Aedes aegypti from oxidative stress and increases midgut infection prevalence of Dengue but not Zika

“…Additionally, genes that conventionally are not considered (or labeled) immune genes, such as lipid and redox metabolism, are also known to influence mosquito-arbovirus interactions and should not be overlooked [8,27,50]. Little is known about the molecular aspects of the interaction between Aedes aegypti and Zika, and antiviral mechanisms described for other flaviviruses will likely be involved [51].…”