Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis

Chen, Zhi; Wang, Wei; Liang, Juhua; Wang, Jinhe; Feng, Shisheng; Zhang, Guangyu

doi:10.1186/s12890-015-0049-4

Cited by 25 publications

(15 citation statements)

References 32 publications

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“…The prevalence of TLR-9 genotypes for C-1237T, C-1486T, and C+2848T polymorphisms in healthy controls was comparable with earlier reports in Chinese population. [8][9][10][11][12] The prevalence of homozygous mutant (TT) for TLR-9 C-1237T polymorphism was significantly higher when compared to other genotypes, which is in line with earlier studies. 10,11 The high prevalence of heterozygotes or homozygous mutant in various populations has been attributed to the local selection pressure of several infectious diseases.…”

Section: Discussionsupporting

confidence: 90%

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Mai

Zhu

2018

Eur J Inflamm

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Helicobacter pylori infections have been one of the major factors associated with gastroduodenal ulcer. Toll-like receptors (TLRs) of human recognize mycobacterium-induced immune response and protect subjects from disease pathogenesis. Variants in TLR genes are believed to influence immune responses to H. pylori and clinical severity. TLR-9 polymorphisms have been associated with susceptibility to gastroduodenal ulcer in different populations. In this study, we investigate the role of common TLR-9 variants in susceptibility/resistance to the development of gastroduodenal ulcer in a Chinese cohort. The present hospital-based case-control study enrolled 580 patients with abdominal discomfort, and based on endoscopic investigation, the patients were categorized into (1) gastric ulcer (n = 154), (2) duodenal ulcer (n = 70), (3) gastric and duodenal ulcers (n = 25), (4) gastritis (n = 195), and (5) healthy stomach (n = 136). A total of 520 healthy controls from similar geographical areas were enrolled as controls. TLR-9 (C-1237T, C-1486T, and G+2848A) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in both healthy controls and patients were quantified by enzyme-linked immunosorbent assay (ELISA). Furthermore, messenger RNA (mRNA) expressions of TNFα, IL-6, and IL-1β in biopsy tissues were quantified by real-time polymerase chain reaction (RT-PCR). The prevalence of TLR-9+2848 heterozygotes (CT) was significantly higher in gastroduodenal ulcer patients compared to healthy controls. Sub-categorization of patients revealed higher prevalence of heterozygotes of TLR-9 C+2848T and C-1486T polymorphisms in patients with gastric ulcer (GU), duodenal ulcer (DU), and those with both gastric and duodenal ulcers (GDU) when compared to controls. Patients displayed higher plasma cytokine levels than healthy controls. TLR-9 polymorphisms (C+2848T and C-1486T) correlated with altered cytokine expression in biopsy tissues and their plasma levels. In conclusion, TLR-9 (C+2848T and C-1486T) polymorphisms are associated with gastroduodenal ulcer and correlated with altered cytokine levels.

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Section: Discussionsupporting

confidence: 90%

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Mai

Zhu

2018

Eur J Inflamm

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“…TLR9 gene with its 2 exons is located on chromosome 3p21.2 in humans. TLR9 gene polymorphism rs352139 is associated with increased risk of Tuberculosis (TB) in Mexican population but it is associated with decreased risk of TB in Indonesian population [418]. A link between TLR9-1237 T/C gene polymorphism and molecular risk for diabetes foot (DF) disease in patients with T2DM is also observed [419].…”

Section: Tlr Polymorphism In Humans and Their Disease Associationmentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

526

346

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The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

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“…The IFA fraction perhaps could deliver MAMPs across membranes. TLR-9 also senses DNA, and appears to play a role during M. tuberculosis infection in mice 38 , and in humans 39 . TLR-9 was also shown to be necessary for full induction of EAE 32,34 .…”

Section: Discussionmentioning

confidence: 99%

Synthetic mycobacterial molecular patterns partially complete Freund’s adjuvant

Dubé

McIntosh

Zarruk

et al. 2020

Sci Rep

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Complete Freund's adjuvant (CFA) has historically been one of the most useful tools of immunologists. Essentially comprised of dead mycobacteria and mineral oil, we asked ourselves what is special about the mycobacterial part of this adjuvant, and could it be recapitulated synthetically? Here, we demonstrate the essentiality of N-glycolylated peptidoglycan plus trehalose dimycolate (both unique in mycobacteria) for the complete adjuvant effect using knockouts and chemical complementation. A combination of synthetic N-glycolyl muramyl dipeptide and minimal trehalose dimycolate motif GlcC14C18 was able to upregulate dendritic cell effectors, plus induce experimental autoimmunity qualitatively similar but quantitatively milder compared to CFA. This research outlines how to substitute CFA with a consistent, molecularly-defined adjuvant which may inform the design of immunotherapeutic agents and vaccines benefitting from cell-mediated immunity. We also anticipate using synthetic microbe-associated molecular patterns (MAMps) to study mycobacterial immunity and immunopathogenesis. Infection with Mycobacterium tuberculosis, or administration of bacille Calmette-Guérin (BCG), normally leads to cell-meditated immunity (CMI) to the corresponding bacterial antigens. The tuberculin skin test is positive when the immune response, a type IV hypersensitivity reaction or delayed-type hypersensitivity (DTH), occurs to tuberculin (a protein extract of M. tuberculosis). This "cutaneous sensitivity" was closely examined in the 1940s using complete Freund's adjuvant (CFA, heat-killed M. tuberculosis in mineral oil plus surfactant) 1,2. These studies provided the first direct evidence for the cellular nature of DTH by transfer from a CFA-immunized guinea pig to a naïve one only through the washed, heat-liable cellular fraction of peritoneal exudates 1,2. It is now known that DTH is mediated specifically by antigen-sensitive T cells. Today, CFA is a 'gold standard' adjuvant for eliciting CMI in research models of autoimmune disease. Notable is the experimental autoimmune encephalomyelitis (EAE) model of T-cell meditated destruction of myelin causing ascending paralysis, used most often to model multiple sclerosis 3,4. CFA is not used in humans because of high reactogenicity 5. We have asked ourselves: what was the impetus for Jules Freund to develop his eponymous adjuvant with M. tuberculosis? For those conducting TB research, it is well appreciated that handling M. tuberculosis (a slow growing, clumping, fastidious, and lethally pathogenic organism) is a significant task per se. So, why did Freund choose to incorporate these bacteria? Effort has been made to describe the microbe-associated molecular patterns (MAMPs) in mycobacteria that drive the adjuvant effect. Evidence has pointed to mycobacterial peptidoglycan (PGN), specifically down to the molecular motif muramyl dipeptide (MDP) 6,7. Mycobacteria are distinct in that they produce the N-glycolyl MDP motif in their cell wall 8-10 and this PGN modification has been shown to be more ...

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Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis

Cited by 25 publications

References 32 publications

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Synthetic mycobacterial molecular patterns partially complete Freund’s adjuvant

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