Parasitic nematode fatty acid- and retinol-binding proteins compromise host immunity by interfering with host lipid signaling pathways
Autor: | Omar S. Akbari, Hideji Fujiwara, Damian Juncaj, Dihong Lu, Martin J. Boulanger, Susan Nguyen, Chaitra Bhat, Harpal Dhillon, Adler R. Dillman, Raghavendran Ramaswamy, Anna Buchman, Naoki Yamanaka, Shyon Nasrolahi, Sophia C. Parks |
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Přispěvatelé: | Fairfax, Keke C |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Bacterial Diseases
Nematoda Biochemistry Animals Genetically Modified Medical Conditions Cell Signaling Medicine and Health Sciences Biology (General) Nematode Infections Immune Response chemistry.chemical_classification 0303 health sciences Drosophila Melanogaster Fatty Acids 030302 biochemistry & molecular biology Eukaryota Animal Models Helminth Proteins Lipids 3. Good health Cell biology Insects Drosophila melanogaster Infectious Diseases Experimental Organism Systems Medical Microbiology Lipid Signaling Drosophila Infection Research Article Signal Transduction Arthropoda QH301-705.5 Immunology Genetically Modified Biology Research and Analysis Methods Fatty Acid-Binding Proteins Microbiology Host-Parasite Interactions 03 medical and health sciences Model Organisms Immune system Immunity Virology Parasitic Diseases Genetics medicine Animals Molecular Biology 030304 developmental biology Host (biology) Prevention Inflammatory and immune system Organisms Biology and Life Sciences Fatty acid Cell Biology Lipid signaling RC581-607 medicine.disease biology.organism_classification Invertebrates Retinol-Binding Proteins Retinol binding protein Nematode Nematode infection chemistry Animal Studies Parasitology Immunologic diseases. Allergy Zoology Entomology |
Zdroj: | PLoS Pathogens, Vol 17, Iss 10, p e1010027 (2021) PLoS pathogens, vol 17, iss 10 PLoS Pathogens PLoS Pathogens, Vol 17, Iss 10 (2021) |
ISSN: | 1553-7374 1553-7366 |
Popis: | 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 nematode infection, yet little is known about their interactions with host tissues. Leveraging the insect parasitic nematode, Steinernema carpocapsae, we describe here the first in vivo study demonstrating that FARs modulate animal immunity, causing an increase in susceptibility to bacterial co-infection. Moreover, we show that FARs dampen key components of the fly immune response including the phenoloxidase cascade and antimicrobial peptide (AMP) production. Our data also reveal 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 an efficient immune response. Collectively, these data support a complex role for FARs in immunosuppression in animals and provide detailed mechanistic insight into parasitism in phylum Nematoda. Author summary 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, found only in nematodes and some bacteria, and are released during nematode 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. |
Databáze: | OpenAIRE |
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