Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1

ABSTRACT Enteroaggregative Escherichia coli (EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering h...

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Autores principales:	Erik J. Boll, Jorge Ayala-Lujan, Rose L. Szabady, Christopher Louissaint, Rachel Z. Smith, Karen A. Krogfelt, James P. Nataro, Fernando Ruiz-Perez, Beth A. McCormick
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Escherichia coli fimbriae inflammation mucin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/56f5e394f9fb42048138ddbf9f651f37
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spelling	oai:doaj.org-article:56f5e394f9fb42048138ddbf9f651f372021-11-15T15:51:29ZEnteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC110.1128/mBio.00717-172150-7511https://doaj.org/article/56f5e394f9fb42048138ddbf9f651f372017-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00717-17https://doaj.org/toc/2150-7511ABSTRACT Enteroaggregative Escherichia coli (EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen. IMPORTANCE EAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs—the principal adhesins of EAEC—in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.Erik J. BollJorge Ayala-LujanRose L. SzabadyChristopher LouissaintRachel Z. SmithKaren A. KrogfeltJames P. NataroFernando Ruiz-PerezBeth A. McCormickAmerican Society for MicrobiologyarticleEscherichia colifimbriaeinflammationmucinMicrobiologyQR1-502ENmBio, Vol 8, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Escherichia coli fimbriae inflammation mucin Microbiology QR1-502
spellingShingle	Escherichia coli fimbriae inflammation mucin Microbiology QR1-502 Erik J. Boll Jorge Ayala-Lujan Rose L. Szabady Christopher Louissaint Rachel Z. Smith Karen A. Krogfelt James P. Nataro Fernando Ruiz-Perez Beth A. McCormick Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1
description	ABSTRACT Enteroaggregative Escherichia coli (EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen. IMPORTANCE EAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs—the principal adhesins of EAEC—in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.
format	article
author	Erik J. Boll Jorge Ayala-Lujan Rose L. Szabady Christopher Louissaint Rachel Z. Smith Karen A. Krogfelt James P. Nataro Fernando Ruiz-Perez Beth A. McCormick
author_facet	Erik J. Boll Jorge Ayala-Lujan Rose L. Szabady Christopher Louissaint Rachel Z. Smith Karen A. Krogfelt James P. Nataro Fernando Ruiz-Perez Beth A. McCormick
author_sort	Erik J. Boll
title	Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1
title_short	Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1
title_full	Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1
title_fullStr	Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1
title_full_unstemmed	Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1
title_sort	enteroaggregative <italic toggle="yes">escherichia coli</italic> adherence fimbriae drive inflammatory cell recruitment via interactions with epithelial muc1
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/56f5e394f9fb42048138ddbf9f651f37
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Enteroaggregative <italic toggle="yes">Escherichia coli</italic> Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1

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