Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection

Toll-like receptors (TLRs) play critical roles in the innate recognition of Mycobacterium tuberculosis (Mtb) by host immune cells. However, controversy has arisen regarding the role of TLR4 in determining the outcomes of Mtb infection. To address this controversy, the function of TLR4 in the inducti...

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Autores principales:	Jaehun Park, Hongmin Kim, Kee Woong Kwon, Hong-Hee Choi, Soon Myung Kang, Jung Joo Hong, Sung Jae Shin
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	mycobacterium tuberculosis tlr4 neutrophil il-10 il-10 receptor Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/c6d1f9554ee64768ba17f5642f5efff8
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spelling	oai:doaj.org-article:c6d1f9554ee64768ba17f5642f5efff82021-11-17T14:21:58ZToll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection2150-55942150-560810.1080/21505594.2020.1766401https://doaj.org/article/c6d1f9554ee64768ba17f5642f5efff82020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1766401https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Toll-like receptors (TLRs) play critical roles in the innate recognition of Mycobacterium tuberculosis (Mtb) by host immune cells. However, controversy has arisen regarding the role of TLR4 in determining the outcomes of Mtb infection. To address this controversy, the function of TLR4 in the induction of an optimal protective immune response against the highly virulent Mtb K-infection was comparatively investigated in C3 H/HeJ (TLR4-deficient mutant) and C3 H/HeN (TLR4-competent wild-type) mice. Interestingly, following Mtb infection, C3 H/HeJ mice showed a more severe disease phenotype than C3 H/HeN mice, exhibiting reduced weight and a marked increase in bacterial burden along with necrotic lung inflammation. Analysis of the immune cell composition revealed significantly increased neutrophils in the lung and significant production of IL-10 accompanied by the impairment of the protective Th1 response in C3 H/HeJ mice. Reducing the neutrophil numbers by treating C3 H/HeJ mice with an anti-Ly6 G monoclonal antibody (mAb) and blocking IL-10 signaling with an anti-IL-10 receptor mAb reduced the excessive lung inflammation and bacterial burden in C3 H/HeJ mice. Therefore, abundant IL-10 signaling and neutrophils have detrimental effects in TLR4-deficient mice during Mtb infection. However, the blockade of IL-10 signaling produced an increase in the CD11bhiLy6 Ghi neutrophil population, but the phenotypes of these neutrophils were different from those of the CD11bintLy6 Gint neutrophils from mice with controlled infections. Collectively, these results show that TLR4 positively contributes to the generation of an optimal protective immunity against Mtb infection. Furthermore, investigating the TLR4-mediated response will provide insight for the development of effective control measures against tuberculosis.Jaehun ParkHongmin KimKee Woong KwonHong-Hee ChoiSoon Myung KangJung Joo HongSung Jae ShinTaylor & Francis Grouparticlemycobacterium tuberculosistlr4neutrophilil-10il-10 receptorInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 430-445 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	mycobacterium tuberculosis tlr4 neutrophil il-10 il-10 receptor Infectious and parasitic diseases RC109-216
spellingShingle	mycobacterium tuberculosis tlr4 neutrophil il-10 il-10 receptor Infectious and parasitic diseases RC109-216 Jaehun Park Hongmin Kim Kee Woong Kwon Hong-Hee Choi Soon Myung Kang Jung Joo Hong Sung Jae Shin Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection
description	Toll-like receptors (TLRs) play critical roles in the innate recognition of Mycobacterium tuberculosis (Mtb) by host immune cells. However, controversy has arisen regarding the role of TLR4 in determining the outcomes of Mtb infection. To address this controversy, the function of TLR4 in the induction of an optimal protective immune response against the highly virulent Mtb K-infection was comparatively investigated in C3 H/HeJ (TLR4-deficient mutant) and C3 H/HeN (TLR4-competent wild-type) mice. Interestingly, following Mtb infection, C3 H/HeJ mice showed a more severe disease phenotype than C3 H/HeN mice, exhibiting reduced weight and a marked increase in bacterial burden along with necrotic lung inflammation. Analysis of the immune cell composition revealed significantly increased neutrophils in the lung and significant production of IL-10 accompanied by the impairment of the protective Th1 response in C3 H/HeJ mice. Reducing the neutrophil numbers by treating C3 H/HeJ mice with an anti-Ly6 G monoclonal antibody (mAb) and blocking IL-10 signaling with an anti-IL-10 receptor mAb reduced the excessive lung inflammation and bacterial burden in C3 H/HeJ mice. Therefore, abundant IL-10 signaling and neutrophils have detrimental effects in TLR4-deficient mice during Mtb infection. However, the blockade of IL-10 signaling produced an increase in the CD11bhiLy6 Ghi neutrophil population, but the phenotypes of these neutrophils were different from those of the CD11bintLy6 Gint neutrophils from mice with controlled infections. Collectively, these results show that TLR4 positively contributes to the generation of an optimal protective immunity against Mtb infection. Furthermore, investigating the TLR4-mediated response will provide insight for the development of effective control measures against tuberculosis.
format	article
author	Jaehun Park Hongmin Kim Kee Woong Kwon Hong-Hee Choi Soon Myung Kang Jung Joo Hong Sung Jae Shin
author_facet	Jaehun Park Hongmin Kim Kee Woong Kwon Hong-Hee Choi Soon Myung Kang Jung Joo Hong Sung Jae Shin
author_sort	Jaehun Park
title	Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection
title_short	Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection
title_full	Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection
title_fullStr	Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection
title_full_unstemmed	Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection
title_sort	toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent mycobacterium tuberculosis k infection
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/c6d1f9554ee64768ba17f5642f5efff8
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Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent Mycobacterium tuberculosis K infection

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