Host- and Helminth-Derived Endocannabinoids That Have Effects on Host Immunity Are Generated during Infection.

Animals; Cytokines/metabolism; Disease Models, Animal; Endocannabinoids/metabolism; Host-Pathogen Interactions; Immunologic Factors/metabolism; Intestines/pathology; Leukocytes, Mononuclear/immunology; Lung/pathology; Mass Spectrometry; Mice; Nippostrongylus/chemistry/growth & development/metabolism; Parasite Egg Count; Parasite Load; Strongylida Infections/immunology/pathology; endocannabinoid; gastrointestinal helminth; nematode

Abstract :

[en] Helminths have coevolved with their hosts, resulting in the development of specialized host immune mechanisms and parasite-specific regulatory products. Identification of new pathways that regulate helminth infection could provide a better understanding of host-helminth interaction and may identify new therapeutic targets for helminth infection. Here we identify the endocannabinoid system as a new mechanism that influences host immunity to helminths. Endocannabinoids are lipid-derived signaling molecules that control important physiologic processes, such as feeding behavior and metabolism. Following murine infection with Nippostrongylus brasiliensis, an intestinal nematode with a life cycle similar to that of hookworms, we observed increased levels of endocannabinoids (2-arachidonoylglycerol [2-AG] or anandamide [AEA]) and the endocannabinoid-like molecule oleoylethanolamine (OEA) in infected lung and intestine. To investigate endocannabinoid function in helminth infection, we employed pharmacological inhibitors of cannabinoid subtype receptors 1 and 2 (CB1R and CB2R). Compared to findings for vehicle-treated mice, inhibition of CB1R but not CB2R resulted in increased N. brasiliensis worm burden and egg output, associated with significantly decreased expression of the T helper type 2 cytokine interleukin 5 (IL-5) in intestinal tissue and splenocyte cultures. Strikingly, bioinformatic analysis of genomic and transcriptome sequencing (RNA-seq) data sets identified putative genes encoding endocannabinoid biosynthetic and degradative enzymes in many parasitic nematodes. To test the novel hypothesis that helminth parasites produce their own endocannabinoids, we measured endocannabinoid levels in N. brasiliensis by mass spectrometry and quantitative PCR and found that N. brasiliensis parasites produced endocannabinoids, especially at the infectious larval stage. To our knowledge, this is the first report of helminth- and host-derived endocannabinoids that promote host immune responses and reduce parasite burden.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Batugedara, Hashini Maneesha ; Université de Liège - ULiège > I3-Cellular and Molecular Immunology

Argueta, Donovan

Jang, Jessica C.

Lu, Dihong

Macchietto, Marissa

Kaur, Jaspreet

Ge, Shaokui

Dillman, Adler R.

DiPatrizio, Nicholas V.

Nair, Meera G.

Language :

English

Title :

Host- and Helminth-Derived Endocannabinoids That Have Effects on Host Immunity Are Generated during Infection.

Publication date :

2018

Journal title :

Infection and Immunity

ISSN :

0019-9567

eISSN :

1098-5522

Publisher :

American Society for Microbiology, Washington, United States - District of Columbia

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 27 May 2019

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37 (1 by ULiège)

Number of downloads

59 (1 by ULiège)

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