<i>Mycoplasma genitalium</i>-Derived Lipid-Associated Membrane Proteins Activate NF-κB through Toll-Like Receptors 1, 2, and 6 and CD14 in a MyD88-Dependent Pathway

He, Jun; You, Xiaoxing; Zeng, Yanhua; Yu, Min; Zuo, Lingling; Wu, Yimou

doi:10.1128/cvi.00281-09

Cited by 61 publications

(63 citation statements)

References 53 publications

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“…These lipoproteins, by interacting with "Toll-like", or TLR receptors, play an essential role in the initiation of the inflammatory response, inducing the activation of the NF-B pathway. The authors of an in vitro study proved that LAMP derived from M. genitalium activated NF-B via TLR1, TLR2 and TLR6 [20], allowing recruiting and activation of monocytes and macrophages in the cervical and vaginal mucosa [19].…”

Section: Pathogenesismentioning

confidence: 99%

Mycoplasma genitalium, an emerging sexually transmitted pathogen

Cazanave

Manhart

Bebear

2012

Médecine et Maladies Infectieuses

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Section: Pathogenesismentioning

confidence: 99%

Mycoplasma genitalium, an emerging sexually transmitted pathogen

Cazanave

Manhart

Bebear

2012

Médecine et Maladies Infectieuses

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“…Many mycoplasmal lipoproteins have been reported to be involved in adhesion to host cells but also in the recognition by the host immune system (1). Indeed, mycoplasmal lipoproteins can act as proinflammatory factors and can stimulate human macrophages and human dendritic cells (hDCs), induce cytokine production, activate NF-B, and polarize the adaptive immune response (2)(3)(4)(5)(6)(7)(8). Nondenaturing detergent extracts, such as Triton X-114 (TX-114) extracts enriched with mycoplasmal lipoproteins, were shown to have modulatory capacities (2,5,6,9,10).…”

mentioning

confidence: 99%

Interaction of Mycoplasma hominis PG21 with Human Dendritic Cells: Interleukin-23-Inducing Mycoplasmal Lipoproteins and Inflammasome Activation of the Cell

et al. 2017

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Mycoplasma hominis lacks a cell wall, and lipoproteins anchored to the extracellular side of the plasma membrane are in direct contact with the host components. A Triton X-114 extract of M. hominis enriched with lipoproteins was shown to stimulate the production of interleukin-23 (IL-23) by human dendritic cells (hDCs). The inflammasome activation of the host cell has never been reported upon M. hominis infection. We studied here the interaction between M. hominis PG21 and hDCs by analyzing both the inflammation-inducing mycoplasmal lipoproteins and the inflammasome activation of the host cell. IL-23-inducing lipoproteins were determined using a sequential extraction strategy with two nondenaturing detergents, Sarkosyl and Triton X-114, followed by SDS-PAGE separation and mass spectrometry identification. The activation of the hDC inflammasome was assessed using PCR array and enzyme-linked immunosorbent assay (ELISA). We defined a list of 24 lipoproteins that could induce the secretion of IL-23 by hDCs, 5 with a molecular mass between 20 and 35 kDa and 19 with a molecular mass between 40 and 100 kDa. Among them, lipoprotein MHO_4720 was identified as potentially bioactive, and a synthetic lipopeptide corresponding to the N-terminal part of the lipoprotein was subsequently shown to induce IL-23 release by hDCs. Regarding the hDC innate immune response, inflammasome activation with caspase-dependent production of IL-1β was observed. After 24 h of coincubation of hDCs with M. hominis, downregulation of the NLRP3-encoding gene and of the adaptor PYCARD-encoding gene was noticed. Overall, this study provides insight into both protagonists of the interaction of M. hominis and hDCs. IMPORTANCE Mycoplasma hominis is a human urogenital pathogen involved in gynecologic and opportunistic infections. M. hominis lacks a cell wall, and its membrane contains many lipoproteins that are anchored to the extracellular side of the plasma membrane. In the present study, we focused on the interaction between M. hominis and human dendritic cells and examined both sides of the interaction, the mycoplasmal lipoproteins involved in the activation of the host cell and the immune response of the cell. On the mycoplasmal side, we showed for the first time that M. hominis lipoproteins with high molecular mass were potentially bioactive. On the cell side, we reported an activation of the inflammasome, which is involved in the innate immune response.

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“…Mycoplasma species induce an immune response via a number of different mechanisms. The first involves engagement with the TLRs, notably TLR2 [128][129][130], leading to the up-regulation of IL-12, IFNγ and other pro-inflammatory cytokines [131,132]. Interestingly, Mycoplasma species infection leads to the generation of a wide range of DAMPs including those normally released following cellular necrosis [133].…”

Section: Mycoplasmamentioning

confidence: 99%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

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Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

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Mycoplasma genitalium-Derived Lipid-Associated Membrane Proteins Activate NF-κB through Toll-Like Receptors 1, 2, and 6 and CD14 in a MyD88-Dependent Pathway

Cited by 61 publications

References 53 publications

Mycoplasma genitalium, an emerging sexually transmitted pathogen

Mycoplasma genitalium, an emerging sexually transmitted pathogen

Interaction of Mycoplasma hominis PG21 with Human Dendritic Cells: Interleukin-23-Inducing Mycoplasmal Lipoproteins and Inflammasome Activation of the Cell

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

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