Toll-like receptor-mediated immune responses in intestinal macrophages; implications for mucosal immunity and autoimmune diseases

Zhou, Zejun; Ding, Miao; Huang, Lei; Gilkeson, Gary; Lang, Ren; Jiang, Wei

doi:10.1016/j.clim.2016.09.005

Cited by 20 publications

(12 citation statements)

References 162 publications

(182 reference statements)

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“…If so, multiple microbial products such as RNA, DNA, peptidoglycan and flagellin derived from bacteria, viruses, fungi and other gastrointestinal residents may translocate into systems and cause systemic immune activation [53–55]. Indeed, our recent work shows that monocytes were activated in vivo in women compared to men, and plasma level of soluble CD14, a marker of monocyte activation by LPS, was higher in women relative to men [56], suggesting a role of systemic bacterial products in immune activation and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues

Zhou

Zhang

Ding

et al. 2017

Clinical Immunology

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Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability.

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Section: Discussionmentioning

confidence: 99%

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues

Zhou

Zhang

Ding

et al. 2017

Clinical Immunology

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“…Additionally, the microbiota is critical for induction of intestinal regulatory T cells (Tregs) as they are absent in germ-free mice (Atarashi et al, 2011). Disrupted signaling downstream from the microbiota, such as through loss of toll-like receptor pathways, is thought to drive disease pathology including in IBD (Zhou et al, 2016). We and others have found that the microbiota is required for proper intestinal barrier repair through innate lymphoid cell production of IL-22 (Longman et al, 2014; Ouyang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses

et al. 2018

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The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CXCR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CXCR1 APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.

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“…Macrophages, a key host-defense cell type, recognize invading pathogens via pathogen-associated pattern recognition receptors to initiate anti-infection innate immune responses [ 1 ]. During Mycobacterium tuberculosis ( M. tuberculosis ) infection, Toll-like receptors (TLRs) on the surface of macrophages are shown to recognize pathogens, trigger endocytosis to form phagosomes, produce cytokines, improve cell apoptosis, and thus exert bactericidal activities [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

TLR4-NOX2 axis regulates the phagocytosis and killing of Mycobacterium tuberculosis by macrophages

Wang

et al. 2017

BMC Pulm Med

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BackgroundMacrophages stand at the forefront of both innate and adapted immunity through their capacities to recognize, engulf, and eliminate foreign particles, and to stimulate adapted immune cells. They are also involved in controlling pro- and anti-inflammatory pathways. Macrophage activity against Mycobacterium tuberculosis (M. tuberculosis) has been shown to involve Toll-like receptor (TLR) activation and ROS production. Previous studies have shown that lipopolysaccharide (LPS), through TLR4, could activate macrophages, improve their bactericidal ROS production, and facilitate anti-infective immune responses. We sought to better understand the role of the TLR4-NOX2 axis in macrophage activation during M. tuberculosis infection.MethodsTHP-1 macrophages and PMA primed THP-1 macrophages [THP-1(A)] were treated with LPS and infected by M. tuberculosis. Cells were analyzed by flow cytometry for TLR4 expression, ROS production, phagocytosis, and killing of M. tuberculosis. Western blotting was used to analyze NOX2 expression. Inhibitors of the TLR4-NOX2 pathway were used to assess this pathway’s role in these processes, and their role in LPS activation of macrophages.ResultsWe found that THP1-derived macrophages or PMA primed THP-1 macrophages exhibit higher surface TLR4 levels and increased NOX2 expression levels following LPS treatment. M. tuberculosis infection reduced these levels, but LPS was able to limit the negative effects of M.tb. Additionally, LPS increases THP-1(A) cells’ bactericidal activities including phagocytosis, ROS production, and destruction of M. tuberculosis. Significantly, all of these activities are impaired when TLR4 or NOX2 are inhibited.ConclusionThese studies demonstrate the importance of the TLR4-NOX2 axis in M. tuberculosis elimination by macrophages and may lead to novel therapies for tuberculosis and other bacterial infections.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0517-0) contains supplementary material, which is available to authorized users.

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Toll-like receptor-mediated immune responses in intestinal macrophages; implications for mucosal immunity and autoimmune diseases

Cited by 20 publications

References 162 publications

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues

Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses

TLR4-NOX2 axis regulates the phagocytosis and killing of Mycobacterium tuberculosis by macrophages

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