Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella

Successful bacterial pathogens have evolved to avoid activating an innate immune system in the host that responds to the pathogen through distinct Toll-like receptors (TLRs). The general class of biochemical components that activate TLRs has been studied extensively, but less is known about how TLRs...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kei Amemiya, Jennifer L. Dankmeyer, Robert C. Bernhards, David P. Fetterer, David M. Waag, Patricia L. Worsham, David DeShazer
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TLRs gram-negative live pathogens innate immunity TLR4 suppression TLR5 activation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7b8d0c605ec6434596bda02c04bdec75
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7b8d0c605ec6434596bda02c04bdec75
record_format	dspace
spelling	oai:doaj.org-article:7b8d0c605ec6434596bda02c04bdec752021-11-30T14:09:08ZActivation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella2235-298810.3389/fcimb.2021.745325https://doaj.org/article/7b8d0c605ec6434596bda02c04bdec752021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.745325/fullhttps://doaj.org/toc/2235-2988Successful bacterial pathogens have evolved to avoid activating an innate immune system in the host that responds to the pathogen through distinct Toll-like receptors (TLRs). The general class of biochemical components that activate TLRs has been studied extensively, but less is known about how TLRs interact with the class of compounds that are still associated with the live pathogen. Accordingly, we examined the activation of surface assembled TLR 2, 4, and 5 with live Tier 1 Gram-negative pathogens that included Yersinia pestis (plague), Burkholderia mallei (glanders), Burkholderia pseudomallei (melioidosis), and Francisella tularensis (tularemia). We found that Y. pestis CO92 grown at 28°C activated TLR2 and TLR4, but at 37°C the pathogen activated primarily TLR2. Although B. mallei and B. pseudomallei are genetically related, the former microorganism activated predominately TLR4, while the latter activated predominately TLR2. The capsule of wild-type B. pseudomallei 1026b was found to mitigate the activation of TLR2 and TLR4 when compared to a capsule mutant. Live F. tularensis (Ft) Schu S4 did not activate TLR2 or 4, although the less virulent Ft LVS and F. novicida activated only TLR2. B. pseudomallei purified flagellin or flagella attached to the microorganism activated TLR5. Activation of TLR5 was abolished by an antibody to TLR5, or a mutation of fliC, or elimination of the pathogen by filtration. In conclusion, we have uncovered new properties of the Gram-negative pathogens, and their interaction with TLRs of the host. Further studies are needed to include other microorganism to extend our observations with their interaction with TLRs, and to the possibility of leading to new efforts in therapeutics against these pathogens.Kei AmemiyaJennifer L. DankmeyerRobert C. BernhardsDavid P. FettererDavid M. WaagPatricia L. WorshamDavid DeShazerFrontiers Media S.A.articleTLRsgram-negativelive pathogensinnate immunityTLR4 suppressionTLR5 activationMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TLRs gram-negative live pathogens innate immunity TLR4 suppression TLR5 activation Microbiology QR1-502
spellingShingle	TLRs gram-negative live pathogens innate immunity TLR4 suppression TLR5 activation Microbiology QR1-502 Kei Amemiya Jennifer L. Dankmeyer Robert C. Bernhards David P. Fetterer David M. Waag Patricia L. Worsham David DeShazer Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella
description	Successful bacterial pathogens have evolved to avoid activating an innate immune system in the host that responds to the pathogen through distinct Toll-like receptors (TLRs). The general class of biochemical components that activate TLRs has been studied extensively, but less is known about how TLRs interact with the class of compounds that are still associated with the live pathogen. Accordingly, we examined the activation of surface assembled TLR 2, 4, and 5 with live Tier 1 Gram-negative pathogens that included Yersinia pestis (plague), Burkholderia mallei (glanders), Burkholderia pseudomallei (melioidosis), and Francisella tularensis (tularemia). We found that Y. pestis CO92 grown at 28°C activated TLR2 and TLR4, but at 37°C the pathogen activated primarily TLR2. Although B. mallei and B. pseudomallei are genetically related, the former microorganism activated predominately TLR4, while the latter activated predominately TLR2. The capsule of wild-type B. pseudomallei 1026b was found to mitigate the activation of TLR2 and TLR4 when compared to a capsule mutant. Live F. tularensis (Ft) Schu S4 did not activate TLR2 or 4, although the less virulent Ft LVS and F. novicida activated only TLR2. B. pseudomallei purified flagellin or flagella attached to the microorganism activated TLR5. Activation of TLR5 was abolished by an antibody to TLR5, or a mutation of fliC, or elimination of the pathogen by filtration. In conclusion, we have uncovered new properties of the Gram-negative pathogens, and their interaction with TLRs of the host. Further studies are needed to include other microorganism to extend our observations with their interaction with TLRs, and to the possibility of leading to new efforts in therapeutics against these pathogens.
format	article
author	Kei Amemiya Jennifer L. Dankmeyer Robert C. Bernhards David P. Fetterer David M. Waag Patricia L. Worsham David DeShazer
author_facet	Kei Amemiya Jennifer L. Dankmeyer Robert C. Bernhards David P. Fetterer David M. Waag Patricia L. Worsham David DeShazer
author_sort	Kei Amemiya
title	Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella
title_short	Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella
title_full	Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella
title_fullStr	Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella
title_full_unstemmed	Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella
title_sort	activation of toll-like receptors by live gram-negative bacterial pathogens reveals mitigation of tlr4 responses and activation of tlr5 by flagella
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7b8d0c605ec6434596bda02c04bdec75
work_keys_str_mv	AT keiamemiya activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella AT jenniferldankmeyer activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella AT robertcbernhards activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella AT davidpfetterer activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella AT davidmwaag activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella AT patricialworsham activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella AT daviddeshazer activationoftolllikereceptorsbylivegramnegativebacterialpathogensrevealsmitigationoftlr4responsesandactivationoftlr5byflagella
_version_	1718406513142267904

Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella

Ejemplares similares