Proteomics

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Staphylococcus aureus Mediated Tolerance Induction in Human Monocytes is accompanied with Specific Alterations in Membrane Receptor Expression


ABSTRACT: Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET). The tolerant state of monocytes is accompanied by cell surface and other glycoprotein expression changes induced by the activation of Toll-like receptors (TLRs). In this study, we aimed to characterize the cellular state of human monocytes stimulated with Gram-positive Staphylococcus aureus and TLR2 ligands. We analyzed gene expression changes induced by S. aureus after 2 and 24 hours by amplicon sequencing (RNA-AmpliSeq) and compared the pro-inflammatory response after 2 hours of stimulation to the to the response in re-stimulation experiments after the first stimulus. In parallel, glycoprotein expression changes in human monocytes after 24 hours of S. aureus stimulation were analyzed by proteomics and compared to stimulation experiments with TLR2 ligands Malp-2 and Pam3Cys and TLR4 ligand LPS. The results demonstrate that monocytes stimulated with S. aureus and TLR ligands entered the tolerant cell state after activation. Compared to TLR agonist mediated activation and tolerization of monocytes, glycoprotein expression changes induced by S. aureus stimulation revealed significant differences in receptor expression profiles. We report a glycoprotein expression profile characteristic for PAMP and S. aureus tolerized human monocytes. Finally, we analyzed peripheral blood monocytes of patients with S. aureus bloodstream infection for inflammatory responses in vitro and for their glycoprotein expression profiles. RNA-AmpliSeq data from patient-derived monocytes demonstrated that the cells were pro-inflammatory responsive to S. aureus stimulation and expressed higher level of CD44 mRNA, while other markers of the tolerant cell state were not detected.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Blood

DISEASE(S): Disease Free

SUBMITTER: Mario Müller  

LAB HEAD: Hortense Slevogt

PROVIDER: PXD036036 | Pride | 2023-05-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Deamidation__N_Sites.txt Txt
Mono1_LPS_MMP_nr1.raw Raw
Mono1_LPS_MMP_nr2.raw Raw
Mono1_LPS_MMP_nr3.raw Raw
Mono1_Malp2_24h_MMP_nr1.raw Raw
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Publications

<i>Staphylococcus aureus</i> induces tolerance in human monocytes accompanied with expression changes of cell surface markers.

Müller Mario M MM   Baldauf Christian C   Hornischer Stella S   Klassert Tilman E TE   Schneegans Antony A   Behnert Andrea A   Pletz Mathias W MW   Hagel Stefan S   Slevogt Hortense H  

Frontiers in immunology 20230331


Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET), associated with the pathogenesis of sepsis. In this study, we aimed to characterize the cellular state of human monocytes from healthy donors stimulated with <i>Staphylococcus aureus</i> in comparison to TLR2-specific ligands. We analyzed <i>S. aureus</i> induced gene expres  ...[more]

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