Surface Lipoproteome of
            <i>Mycoplasma Hominis</i>
            PG21 and Differential Expression After Contact with Human Dendritic Cells

Goret, Julien; Roy, Chloé Le; Touati, Arabella; Mesureur, Jennifer; Renaudin, H.; Claverol, Stéphane; Bebear, Cécile; Béven, Laure; Pereyre, Sabine

doi:10.2217/fmb.15.130

Cited by 11 publications

(11 citation statements)

References 44 publications

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“…Lipoproteins were considered nonfragmented when the AMM was close to that calculated on the basis of their predicted molecular mass. A total of 26 of the 48 M. hominis predicted lipoproteins (19,20) were detected, i.e., 54.2% of the lipoproteins predicted in silico (Table 1). Two lipoproteins, MHO_1640 and MHO_3620, which were solely present in the E2 and E6 eluates, which did not induce IL-23 release from hDCs, were not considered to be bioactive.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…Proteins from the eluates of interest were identified as previously described by liquid chromatographytandem mass spectrometry (LC-MS/MS) (19).…”

Section: Methodsmentioning

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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“…With this, IbpM exhibits all important abilities to subvert the host immune system. Beside other mycoplasmal lipoproteins that facilitate surveillance in the host (Citti and Rosengarten, 1997;Chambaud et al, 1999;Goret et al, 2016), IbpM is a new target for better understanding virulence of M. pneumoniae. The functions of IbpM in vivo and its implication in virulence, especially potential immunomodulatory effects need to be elucidated in the future.…”

Section: Resultsmentioning

confidence: 99%

Characterization of an Immunoglobulin Binding Protein (IbpM) From Mycoplasma pneumoniae

et al. 2020

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Bacteria evolved many ways to invade, colonize and survive in the host tissue. Such complex infection strategies of other bacteria are not present in the cell-wall less Mycoplasmas. Due to their strongly reduced genomes, these bacteria have only a minimal metabolism. Mycoplasma pneumoniae is a pathogenic bacterium using its virulence repertoire very efficiently, infecting the human lung. M. pneumoniae can cause a variety of conditions including fever, inflammation, atypical pneumoniae, and even death. Due to its strongly reduced metabolism, M. pneumoniae is dependent on nutrients from the host and aims to persist as long as possible, resulting in chronic diseases. Mycoplasmas evolved strategies to subvert the host immune system which involve proteins fending off immunoglobulins (Igs). In this study, we investigated the role of MPN400 as the putative factor responsible for Ig-binding and host immune evasion. MPN400 is a cell-surface localized protein which binds strongly to human IgG, IgA, and IgM. We therefore named the protein MPN400 immunoglobulin binding protein of Mycoplasma (IbpM). A strain devoid of IbpM is slightly compromised in cytotoxicity. Taken together, our study indicates that M. pneumoniae uses a refined mechanism for immune evasion.

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“…There are 43 predicted lipoproteins in the PG21 genome, the type strain of M . hominis [ 1 ], 84% of which have been identified at a protein level [ 14 ]. In an in vitro infection model 38 lipoprotein genes were differentially expressed after 4 and 24 h of co-incubation with human dendritic cells (hDC).…”

Section: Discussionmentioning

confidence: 99%

“…In 2016, Goret et al published a large-scale expression study of M . hominis lipoprotein genes upon contact with human dendritic cells (hDCs) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Validation of a novel Mho microarray for a comprehensive characterisation of the Mycoplasma hominis action in HeLa cell infection

et al. 2017

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Mycoplasma hominis is the second smallest facultative pathogen of the human urogenital tract. With less than 600 protein-encoding genes, it represents an ideal model organism for the study of host-pathogen interactions. For a comprehensive characterisation of the M. hominis action in infection a customized Mho microarray, which was based on two genome sequences (PG21 and LBD-4), was designed to analyze the dynamics of the mycoplasma transcriptome during infection and validated for M. hominis strain FBG. RNA preparation was evaluated and adapted to ensure the highest recovery of mycoplasmal mRNAs from in vitro HeLa cell infection assays. Following cRNA hybridization, the read-out strategy of the hybridization results was optimized and confirmed by RT-PCR. A statistically robust infection assay with M. hominis strain FBG enabled the identification of differentially regulated key effector molecules such as critical cytoadhesins (4 h post infection (pI)), invasins (48 h pI) and proteins associated with establishing chronic infection of the host (336 h pI). Of the 294 differentially regulated genes (>2-fold) 128 (43.5%) encoded hypothetical proteins, including lipoproteins that seem to play a central role as virulence factors at each stage of infection: P75 as a novel cytoadhesin candidate, which is also differentially upregulated in chronic infection; the MHO_2100 protein, a postulated invasin and the MHO_730-protein, a novel ecto-nuclease and domain of an ABC transporter, the function of which in chronic infection has still to be elucidated. Implementation of the M. hominis microarray strategy led to a comprehensive identification of to date unknown candidates for virulence factors at relevant stages of host cell infection.

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Surface Lipoproteome of Mycoplasma Hominis PG21 and Differential Expression After Contact with Human Dendritic Cells

Abstract: M. hominis regulates lipoprotein gene expression and may use species-specific mechanisms during the host colonization process.

Cited by 11 publications

References 44 publications

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

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

Characterization of an Immunoglobulin Binding Protein (IbpM) From Mycoplasma pneumoniae

Validation of a novel Mho microarray for a comprehensive characterisation of the Mycoplasma hominis action in HeLa cell infection

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