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Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes
Campylobacter jejuni is a leading cause of gastroenteritis that has been causally linked with development of the autoimmune peripheral neuropathy Guillain Barré Syndrome (GBS). Previously, we showed that C. jejuni isolates from human enteritis patients induced Type1/17-cytokine dependent colitis in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037470/ https://www.ncbi.nlm.nih.gov/pubmed/35442154 http://dx.doi.org/10.1080/19490976.2022.2064706 |
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author | Malik, Ankit Brudvig, Jean M. Gadsden, Barbie J. Ethridge, Alexander D. Mansfield, Linda S. |
author_facet | Malik, Ankit Brudvig, Jean M. Gadsden, Barbie J. Ethridge, Alexander D. Mansfield, Linda S. |
author_sort | Malik, Ankit |
collection | PubMed |
description | Campylobacter jejuni is a leading cause of gastroenteritis that has been causally linked with development of the autoimmune peripheral neuropathy Guillain Barré Syndrome (GBS). Previously, we showed that C. jejuni isolates from human enteritis patients induced Type1/17-cytokine dependent colitis in interleukin-10 (IL-10)(−/−) mice, while isolates from GBS patients colonized these mice without colitis but instead induced autoantibodies that cross-reacted with the sialylated oligosaccharide motifs on the LOS of GBS-associated C. jejuni and the peripheral nerve gangliosides. We show here that infection of IL-10(−/−) mice with the GBS but not the colitis isolate led to sciatic nerve inflammation and abnormal gait and hind limb movements, with character and timing consistent with this syndrome in humans. Autoantibody responses and associated nerve histologic changes were dependent on IL-4 production by CD4 T cells. We further show that Siglec-1 served as a central antigen presenting cell receptor mediating the uptake of the GBS isolates via interaction with the sialylated oligosaccharide motifs found specifically on the LOS of GBS-associated C. jejuni, and the ensuing T cell differentiation and autoantibody elicitation. Sialylated oligosaccharide motifs on the LOS of GBS-associated C. jejuni therefore acted as both the Siglec-1-ligand for phagocytosis, as well as the epitope for autoimmunity. Overall, we present a mouse model of an autoimmune disease induced directly by a bacterium that is dependent upon Siglec-1 and IL-4. We also demonstrate the negative regulatory role of IL-10 in C. jejuni induced autoimmunity and provide IL-4 and Siglec-1 blockade as potential therapeutic interventions against GBS. |
format | Online Article Text |
id | pubmed-9037470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-90374702022-04-26 Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes Malik, Ankit Brudvig, Jean M. Gadsden, Barbie J. Ethridge, Alexander D. Mansfield, Linda S. Gut Microbes Research Paper Campylobacter jejuni is a leading cause of gastroenteritis that has been causally linked with development of the autoimmune peripheral neuropathy Guillain Barré Syndrome (GBS). Previously, we showed that C. jejuni isolates from human enteritis patients induced Type1/17-cytokine dependent colitis in interleukin-10 (IL-10)(−/−) mice, while isolates from GBS patients colonized these mice without colitis but instead induced autoantibodies that cross-reacted with the sialylated oligosaccharide motifs on the LOS of GBS-associated C. jejuni and the peripheral nerve gangliosides. We show here that infection of IL-10(−/−) mice with the GBS but not the colitis isolate led to sciatic nerve inflammation and abnormal gait and hind limb movements, with character and timing consistent with this syndrome in humans. Autoantibody responses and associated nerve histologic changes were dependent on IL-4 production by CD4 T cells. We further show that Siglec-1 served as a central antigen presenting cell receptor mediating the uptake of the GBS isolates via interaction with the sialylated oligosaccharide motifs found specifically on the LOS of GBS-associated C. jejuni, and the ensuing T cell differentiation and autoantibody elicitation. Sialylated oligosaccharide motifs on the LOS of GBS-associated C. jejuni therefore acted as both the Siglec-1-ligand for phagocytosis, as well as the epitope for autoimmunity. Overall, we present a mouse model of an autoimmune disease induced directly by a bacterium that is dependent upon Siglec-1 and IL-4. We also demonstrate the negative regulatory role of IL-10 in C. jejuni induced autoimmunity and provide IL-4 and Siglec-1 blockade as potential therapeutic interventions against GBS. Taylor & Francis 2022-04-20 /pmc/articles/PMC9037470/ /pubmed/35442154 http://dx.doi.org/10.1080/19490976.2022.2064706 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Malik, Ankit Brudvig, Jean M. Gadsden, Barbie J. Ethridge, Alexander D. Mansfield, Linda S. Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes |
title | Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes |
title_full | Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes |
title_fullStr | Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes |
title_full_unstemmed | Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes |
title_short | Campylobacter jejuni induces autoimmune peripheral neuropathy via Sialoadhesin and Interleukin-4 axes |
title_sort | campylobacter jejuni induces autoimmune peripheral neuropathy via sialoadhesin and interleukin-4 axes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037470/ https://www.ncbi.nlm.nih.gov/pubmed/35442154 http://dx.doi.org/10.1080/19490976.2022.2064706 |
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