RT Journal Article
SR Electronic
T1 Parasitic nematode fatty acid- and retinol-binding proteins compromise host immunity by interfering with host lipid signaling pathways
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.25.436866
DO 10.1101/2021.03.25.436866
A1 Sophia C. Parks
A1 Chau Nguyen
A1 Shyon Nasrolahi
A1 Damian Juncaj
A1 Dihong Lu
A1 Raghavendran Ramaswamy
A1 Harpal Dhillon
A1 Anna Buchman
A1 Omar S. Akbari
A1 Naoki Yamanaka
A1 Martin J. Boulanger
A1 Adler R. Dillman
YR 2021
UL http://biorxiv.org/content/early/2021/03/25/2021.03.25.436866.abstract
AB Parasitic nematodes cause significant morbidity and mortality globally. Excretory/secretory products (ESPs) such as fatty acid- and retinol- binding proteins (FARs) are hypothesized to suppress host immunity during infection, yet little is known about their interactions with host tissues. Leveraging the insect parasitic nematode, Steinernema carpocapsae, we provide the first in vivo study that shows FARs modulate animal immunity, causing an increase in susceptibility to bacterial infection. Next we determined that FARs dampen various aspects of the fly immune response including the phenoloxidase cascade and antimicrobial peptide (AMP) production. Finally, we found that FARs deplete lipid signaling precursors in vivo as well as bind to these fatty acids in vitro, suggesting that FARs elicit their immunomodulatory effects by altering the availability of lipid signaling molecules necessary for a functional immune response. Collectively, these data reveal a complex role for FARs in immunosuppression and provide detailed mechanistic insight into parasitism in phylum Nematoda.Significance A central aspect of parasitic nematode success is their ability to modify host biology, including evasion and/or subversion of host immunity. Modulation of host biology and the pathology caused by parasitic nematodes is largely effected through the release of proteins and small molecules. There are hundreds of proteins released by nematodes during an infection and few have been studied in detail. Fatty acid- and retinol-binding proteins (FARs) are a unique protein family released during infection. We report that nematode FARs from S. carpocapsae, C. elegans and A. ceylanicum dampen fly immunity decreasing resistance to infection. Mechanistically, this is achieved through modulation of the phenoloxidase cascade and antimicrobial peptide production. Furthermore, FARs alter the availability of lipid immune signaling precursors in vivo and show binding specificity in vitro.Graphical AbstractCompeting Interest StatementThe authors have declared no competing interest.