<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity

ABSTRACT Chlamydia trachomatis is the most common bacterial cause of sexually transmitted infections. C. trachomatis sexually transmitted infections are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as the C. trachomatis oute...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chunfu Yang, Michael Briones, Janice Chiou, Lei Lei, Michael John Patton, Li Ma, Grant McClarty, Harlan D. Caldwell
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	caspase-11 chlamydia inflammation lipopolysaccharide TLR4 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d32b2dfcb3b540c09fa6a6592f08a802
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d32b2dfcb3b540c09fa6a6592f08a802
record_format	dspace
spelling	oai:doaj.org-article:d32b2dfcb3b540c09fa6a6592f08a8022021-11-15T15:55:24Z<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity10.1128/mBio.00595-192150-7511https://doaj.org/article/d32b2dfcb3b540c09fa6a6592f08a8022019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00595-19https://doaj.org/toc/2150-7511ABSTRACT Chlamydia trachomatis is the most common bacterial cause of sexually transmitted infections. C. trachomatis sexually transmitted infections are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as the C. trachomatis outer membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we studied the ability of chlamydial LPS to activate the proinflammatory canonical and noncanonical inflammasome pathways in mouse bone marrow-derived macrophages (BMDM). We show, in comparison to Escherichia coli LPS, that C. trachomatis LPS-treated BMDM produce significantly less IL-6, TNF, and type I interferon mRNA, indicating that downstream signaling through the canonical TLR4 myddosome and triffosome pathways was blocked. We confirmed this in C. trachomatis LPS-treated BMDM by showing the lack of NF-κB and IRF3 phosphorylation, respectively. Interestingly, C. trachomatis LPS bound CD14 and promoted its endocytosis; however; it did not promote efficient TLR4/MD-2 dimerization or endocytosis, known requirements for myddosome and triffosome signaling pathways. We further found that transfection of BMDM with C. trachomatis LPS did not cause pyroptotic cell ballooning, cytotoxicity, or IL-1β secretion, all characteristic features of noncanonical inflammasome activation. Western blotting confirmed that cytosolic C. trachomatis LPS failed to signal through caspase-11, as shown by the lack of gasdermin D, caspase-1, or IL-1β proteolytic cleavage. We propose that chlamydiae evolved a unique LPS structure as a pathogenic strategy to avoid canonical and noncanonical innate immune signaling and conclude that this strategy might explain the high incidence of asymptomatic infections. IMPORTANCE Chlamydia trachomatis is the most common bacterial cause of sexually transmitted infections (STI). C. trachomatis STI are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as the C. trachomatis outer membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we found that C. trachomatis LPS is not capable of engaging the canonical TLR4/MD-2 or noncanonical caspase-11 inflammatory pathways. The inability of C. trachomatis LPS to trigger innate immunity inflammatory pathways is related to its unique fatty acid structure. Evolutionary modification of the LPS structure likely evolved as a pathogenic strategy to silence innate host defense mechanisms. The findings might explain the high incidence of asymptomatic chlamydial genital infection.Chunfu YangMichael BrionesJanice ChiouLei LeiMichael John PattonLi MaGrant McClartyHarlan D. CaldwellAmerican Society for Microbiologyarticlecaspase-11chlamydiainflammationlipopolysaccharideTLR4MicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	caspase-11 chlamydia inflammation lipopolysaccharide TLR4 Microbiology QR1-502
spellingShingle	caspase-11 chlamydia inflammation lipopolysaccharide TLR4 Microbiology QR1-502 Chunfu Yang Michael Briones Janice Chiou Lei Lei Michael John Patton Li Ma Grant McClarty Harlan D. Caldwell <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity
description	ABSTRACT Chlamydia trachomatis is the most common bacterial cause of sexually transmitted infections. C. trachomatis sexually transmitted infections are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as the C. trachomatis outer membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we studied the ability of chlamydial LPS to activate the proinflammatory canonical and noncanonical inflammasome pathways in mouse bone marrow-derived macrophages (BMDM). We show, in comparison to Escherichia coli LPS, that C. trachomatis LPS-treated BMDM produce significantly less IL-6, TNF, and type I interferon mRNA, indicating that downstream signaling through the canonical TLR4 myddosome and triffosome pathways was blocked. We confirmed this in C. trachomatis LPS-treated BMDM by showing the lack of NF-κB and IRF3 phosphorylation, respectively. Interestingly, C. trachomatis LPS bound CD14 and promoted its endocytosis; however; it did not promote efficient TLR4/MD-2 dimerization or endocytosis, known requirements for myddosome and triffosome signaling pathways. We further found that transfection of BMDM with C. trachomatis LPS did not cause pyroptotic cell ballooning, cytotoxicity, or IL-1β secretion, all characteristic features of noncanonical inflammasome activation. Western blotting confirmed that cytosolic C. trachomatis LPS failed to signal through caspase-11, as shown by the lack of gasdermin D, caspase-1, or IL-1β proteolytic cleavage. We propose that chlamydiae evolved a unique LPS structure as a pathogenic strategy to avoid canonical and noncanonical innate immune signaling and conclude that this strategy might explain the high incidence of asymptomatic infections. IMPORTANCE Chlamydia trachomatis is the most common bacterial cause of sexually transmitted infections (STI). C. trachomatis STI are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as the C. trachomatis outer membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we found that C. trachomatis LPS is not capable of engaging the canonical TLR4/MD-2 or noncanonical caspase-11 inflammatory pathways. The inability of C. trachomatis LPS to trigger innate immunity inflammatory pathways is related to its unique fatty acid structure. Evolutionary modification of the LPS structure likely evolved as a pathogenic strategy to silence innate host defense mechanisms. The findings might explain the high incidence of asymptomatic chlamydial genital infection.
format	article
author	Chunfu Yang Michael Briones Janice Chiou Lei Lei Michael John Patton Li Ma Grant McClarty Harlan D. Caldwell
author_facet	Chunfu Yang Michael Briones Janice Chiou Lei Lei Michael John Patton Li Ma Grant McClarty Harlan D. Caldwell
author_sort	Chunfu Yang
title	<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity
title_short	<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity
title_full	<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity
title_fullStr	<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity
title_full_unstemmed	<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity
title_sort	<named-content content-type="genus-species">chlamydia trachomatis</named-content> lipopolysaccharide evades the canonical and noncanonical inflammatory pathways to subvert innate immunity
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/d32b2dfcb3b540c09fa6a6592f08a802
work_keys_str_mv	AT chunfuyang namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT michaelbriones namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT janicechiou namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT leilei namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT michaeljohnpatton namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT lima namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT grantmcclarty namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity AT harlandcaldwell namedcontentcontenttypegenusspecieschlamydiatrachomatisnamedcontentlipopolysaccharideevadesthecanonicalandnoncanonicalinflammatorypathwaystosubvertinnateimmunity
_version_	1718427180130631680

<named-content content-type="genus-species">Chlamydia trachomatis</named-content> Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity

Ejemplares similares