PT  - JOURNAL ARTICLE
AU  - Sophia C. Parks
AU  - Chau Nguyen
AU  - Shyon Nasrolahi
AU  - Damian Juncaj
AU  - Dihong Lu
AU  - Raghavendran Ramaswamy
AU  - Harpal Dhillon
AU  - Anna Buchman
AU  - Omar S. Akbari
AU  - Naoki Yamanaka
AU  - Martin J. Boulanger
AU  - Adler R. Dillman
TI  - Parasitic nematode fatty acid- and retinol-binding proteins compromise host immunity by interfering with host lipid signaling pathways
AID  - 10.1101/2021.03.25.436866
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.25.436866
4099  - http://biorxiv.org/content/early/2021/03/25/2021.03.25.436866.short
4100  - http://biorxiv.org/content/early/2021/03/25/2021.03.25.436866.full
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.