Cooperative Interactions between Toll-Like Receptor 2 and Toll-Like Receptor 4 in Murine Klebsiella pneumoniae Infections

Jeon, Hee‐Yeon; Park, Jong‐Hyung; Park, Jin‐Il; Kim, Junyoung; Seo, Sun-Min; Ham, Seung‐Hoon; Jeong, Eui‐Suk; Choi, Yang Kyu

doi:10.4014/jmb.1704.04039

Cited by 16 publications

(11 citation statements)

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“…These receptors play crucial roles in host recognition and the NF-B signaling pathway and are used by many lactic acid bacteria to induce anti-inflammatory activity. TLRs and their adaptors are involved in lung defense mechanisms during K. pneumoniae infection (16,17,40,41). In view of these elements, we can hypothesize that L. plantarum CIRM653 interacts with the TLR pathway to block NF-B activation, thereby limiting the lung innate immune response during K. pneumoniae infection.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae

et al. 2019

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Some respiratory infections have been associated with dysbiosis of the intestinal microbiota. The underlying mechanism is incompletely understood, but cross talk between the intestinal microbiota and local immune cells could influence the immune response at distal mucosal sites. This has led to the concept of enhancing respiratory defenses by modulating the intestinal microbiota with exogenous supplementation of beneficial strains. In this study, we examined the effect of Lactobacillus plantarum CIRM653 on the inflammatory response induced by the pathogen Klebsiella pneumoniae. Oral administration of L. plantarum CIRM653 to mice subsequently infected by K. pneumoniae via the nasal route (i) reduced the pulmonary inflammation response, with decreased numbers of lung innate immune cells (macrophages and neutrophils) and cytokines (mouse keratinocyte-derived chemokine [KC], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNF-α]) in the bronchoalveolar fluid, and (ii) induced an immunosuppressive Treg response in lungs. In vitro coincubation of L. plantarum CIRM653 and K. pneumoniae with human dendritic cells and peripheral blood mononuclear cells resulted in decreased Th1 (IL-12p70 and interferon gamma [IFN-γ]) and Th17 (IL-23 and IL-17) and increased Treg (IL-10) cytokine levels compared to those observed for K. pneumoniae-infected cells. Neither K. pneumoniae nor L. plantarum CIRM653 had any effect on cytokine production by intestinal epithelial cells in vitro, but the induction of the NF-κB pathway and IL-8 and IL-6 production by K. pneumoniae in airway epithelial cells was significantly reduced when the pathogen was coincubated with L. plantarum CIRM653. The remote IL-10-mediated modulation of the K. pneumoniae inflammatory response by L. plantarum CIRM653 supports the concept of immunomodulation by beneficial bacteria through the gut-lung axis.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae

et al. 2019

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“…TLR4 might influence the progress of pneumonia (Cai et al, 2015). Jeon et al (2017) suggest that TLR4 is more important in the immune response against K. pneumoniae infection than TLR2. Therefore, TLR4 play cooperative roles in innate immune responses in the lungs that induces systemic inflammation during K. pneumoniae infection.…”

Section: Toll Like Receptor (Tlr4) Detectionmentioning

confidence: 99%

Immunological Study of Klebsiella Pneumoniae Isolated from Pneumoniae Infection Patients

Ali

Alkhudhairy

Tobal

2022

BCS

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This study aimed for isolation and identification of Klebsiella pneumoniae was an opportunistic pathogen responsible for a wide range of clinical syndromes such as pneumonia in both hospital and community settings. Assessment some immune parameter this study was carried out in Al-Diwaniya Teaching Hospital in Al-Diwaniya Province during the period from December 2018 to February 2019. A total of 272 individuals in both sex: 139 males and 133 females, including 210 sputum and blood specimens were collected from patients with pneumonia and 62 blood specimens were collected from healthy persons as a control group. The result of Microbiological tests of sputum was found 120(57.2%) specimens as Gram negative bacteria. From these specimens found 62(51.7%) have been appeared as positive result for K. pneumoniae and represented a major cause for pneumonia in this study, 37(59.7%) of them were males and 25(40.3%) female. 59(95.16%) of K. pneumoniae isolates have capsule when stained negatively with Indian ink. While, 60 (96.77%) isolates were appeared hypermucoviscosity (HVM) phenotype. The level of interferon gamma (IFN-γ) and toll like receptor (TLR4) concentration was measured by using enzyme-linked immunosorbent assay (ELIZA) and was found that IFN-γ is significantly (p ˂0.05) raised in all age groups of patients in comparison to the healthy control groups. The level of IFN-γ in age group (1-10) years recorded high percentage (293.123) compared with other age groups.. On the other hand, the level of TLR4 concentration was found that is significantly (p˂0.05) raised in all age groups of patients in comparison to the healthy control group. The level of TLR4 in age group (51-60) years recorded high percentage (12.993) compared to other age groups.

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“…Table 4 summarizes similar data for the most common fungal infections associated with these syndromes. Bacteria generally activate TLR1, TLR2, TLR4, TLR9, NLRP3 and NOD2 (Table 3) (reviewed in [147], Group A Streptococcal activation [148][149][150][151][152][153][154][155][156], Group B Streptococcal activation [68,147,[157][158][159], Staphylococci [147,151,160,161], Mycobacteria [147,162,163], Klebsiella [164][165][166][167][168][169], Haemophilus [147,149,150,[170][171][172][173][174], Legionella [147,163,175,176], Chlamydia [147,163,[177][178][179]…”

Section: Innate Receptor Activation By Bacterial and Fungal Infectionmentioning

confidence: 99%

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

Root‐Bernstein

2021

IJMS

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Severe COVID-19 is characterized by a “cytokine storm”, the mechanism of which is not yet understood. I propose that cytokine storms result from synergistic interactions among Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR) due to combined infections of SARS-CoV-2 with other microbes, mainly bacterial and fungal. This proposition is based on eight linked types of evidence and their logical connections. (1) Severe cases of COVID-19 differ from healthy controls and mild COVID-19 patients in exhibiting increased TLR4, TLR7, TLR9 and NLRP3 activity. (2) SARS-CoV-2 and related coronaviruses activate TLR3, TLR7, RIG1 and NLRP3. (3) SARS-CoV-2 cannot, therefore, account for the innate receptor activation pattern (IRAP) found in severe COVID-19 patients. (4) Severe COVID-19 also differs from its mild form in being characterized by bacterial and fungal infections. (5) Respiratory bacterial and fungal infections activate TLR2, TLR4, TLR9 and NLRP3. (6) A combination of SARS-CoV-2 with bacterial/fungal coinfections accounts for the IRAP found in severe COVID-19 and why it differs from mild cases. (7) Notably, TLR7 (viral) and TLR4 (bacterial/fungal) synergize, TLR9 and TLR4 (both bacterial/fungal) synergize and TLR2 and TLR4 (both bacterial/fungal) synergize with NLRP3 (viral and bacterial). (8) Thus, a SARS-CoV-2-bacterium/fungus coinfection produces synergistic innate activation, resulting in the hyperinflammation characteristic of a cytokine storm. Unique clinical, experimental and therapeutic predictions (such as why melatonin is effective in treating COVID-19) are discussed, and broader implications are outlined for understanding why other syndromes such as acute lung injury, acute respiratory distress syndrome and sepsis display varied cytokine storm symptoms.

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Cooperative Interactions between Toll-Like Receptor 2 and Toll-Like Receptor 4 in Murine Klebsiella pneumoniae Infections

Cited by 16 publications

References 0 publications

Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae

Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae

Immunological Study of Klebsiella Pneumoniae Isolated from Pneumoniae Infection Patients

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

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