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Nematode asparaginyl-tRNA synthetase resolves intestinal inflammation in mice with T-cell transfer colitis. Clin Vaccine Immunol 2013 Feb;20(2):276-81

Date

12/21/2012

Pubmed ID

23254300

Pubmed Central ID

PMC3571265

DOI

10.1128/CVI.00594-12

Abstract

The therapeutic effects of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) have been demonstrated in both animal and human models. However, the inability of individual well-characterized nematode proteins to recreate these beneficial effects has limited the application of component immunotherapy to human disease. The nematodes that cause chronic human lymphatic filariasis, Brugia malayi and Wuchereria bancrofti, are among the parasites that induce immune suppression. Filarial lymphatic pathology has been shown to involve NF-κB pathway-dependent production of vascular endothelial growth factor (VEGF), and stimulation of VEGF expression has also been reported by interleukin 8 (IL-8) via NF-κB pathways. Previously, we have shown that the filarial asparaginyl-tRNA synthetase (rBmAsnRS) interacts with IL-8 receptors using a combination of extracellular loops that differ from those bound by IL-8. To test the hypothesis that rBmAsnRS might induce an anti-inflammatory effect in vivo, we studied the effects of rBmAsnRS in an established murine colitis model using T-cell transfer mice. T-cell transfer colitis mice treated intraperitoneally with 100 μg of rBmAsnRS four times over 2 weeks showed resolution of cellular infiltration in the colonic mucosa, along with induction of a CD8(+) cellular response. In addition, rBmAsnRS induced a rise in IL-10 production from CD3(+) and lipopolysaccharide (LPS)- and cytosine phosphate guanosine (CPG)-stimulated splenic cells. In summary, this work demonstrates a novel anti-inflammatory nematode protein, supports the hygiene hypothesis, and supports continued refinement of alternative immunotherapies for treatment of IBD.

Author List

Kron MA, Metwali A, Vodanovic-Jankovic S, Elliott D

Author

Michael Kron MD Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aspartate-tRNA Ligase
Brugia malayi
CD3 Complex
CD8-Positive T-Lymphocytes
Colitis
Dendritic Cells
Homeodomain Proteins
Immunotherapy
Inflammation
Inflammation Mediators
Interleukin-10
Interleukin-8
Intestinal Mucosa
Intestines
Lipopolysaccharides
Mice
Mice, Inbred C57BL
NF-kappa B
Piroxicam
RNA, Transfer, Amino Acyl
Receptors, Interleukin-8
Vascular Endothelial Growth Factors
Wuchereria bancrofti
jenkins-FCD Prod-388 89e904233d719332173309c68ab82b0b2a78a3a7