Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based infection model

Siwczak, Fatina; Cseresnyés, Zoltán; Hassan, Mohamed I. Abdelwahab; Aina, Kehinde Oluwasegun; Carlstedt, Swen; Sigmund, Anke; Gröger, Marko; Surewaard, Bas G. J.; Werz, Oliver; Figge, Marc Thilo; Tuchscherr, Lorena; Löffler, Bettina; Mosig, Alexander S.

doi:10.1016/j.biomaterials.2022.121632

Cited by 18 publications

(13 citation statements)

References 68 publications

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“…Salmonella was shown to use the SPI1 effectors for the epigenetic reprogramming of macrophages responsible for bacterial long-term survival [ 59 ]. M2 polarization was shown to favor Staphylococcus aureus survival and further infection [ 60 ]. Obtained results suggested that this strategy was used by L. monocytogenes strains belonging to highly virulent clones.…”

Section: Discussionmentioning

confidence: 99%

Natural Isoforms of Listeria monocytogenes Virulence Factor Inlb Differ in c-Met Binding Efficiency and Differently Affect Uptake and Survival Listeria in Macrophage

Chalenko

Slonova

Kechko

et al. 2023

IJMS

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Listeria monocytogenes virulence factor InlB specifically interacts with the receptors c-Met and gC1q-R. Both receptors are present in non-professional and professional phagocytes, including macrophages. Phylogenetically defined InlB isoforms differently support invasion into non-professional phagocytes. This work deals with the effects of InlB isoforms on L. monocytogenes uptake and intracellular proliferation in human macrophages. Three isoforms of the receptor binding domain (idInlB) were derived from phylogenetically distinct L. monocytogenes strains belonging to the highly virulent CC1 (idInlBCC1), medium-virulence CC7 (idInlBCC7), and low-virulence CC9 (idInlBCC9) clonal complexes. The constant dissociation increased in the order idInlBCC1 << idInlBCC7 < idInlBCC9 for interactions with c-Met, and idInlBCC1 ≈ idInlBCC7 < idInlBCC9 for interactions with gC1q-R. The comparison of uptake and intracellular proliferation of isogenic recombinant strains which expressed full-length InlBs revealed that the strain expressing idInlBCC1 proliferated in macrophages twice as efficiently as other strains. Macrophage pretreatment with idInlBCC1 followed by recombinant L. monocytogenes infection disturbed macrophage functions decreasing pathogen uptake and improving its intracellular multiplication. Similar pretreatment with idInlBCC7 decreased bacterial uptake but also impaired intracellular multiplication. The obtained results demonstrated that InlB impaired macrophage functions in an idInlB isoform-dependent manner. These data suggest a novel InlB function in L. monocytogenes virulence.

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Section: Discussionmentioning

confidence: 99%

Natural Isoforms of Listeria monocytogenes Virulence Factor Inlb Differ in c-Met Binding Efficiency and Differently Affect Uptake and Survival Listeria in Macrophage

Chalenko

Slonova

Kechko

et al. 2023

IJMS

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Section: Liver-centric Microphysiological Systemsmentioning

confidence: 99%

“…Observation of immuno-response in this device noted the limited bacterial clearance capabilities of M2 macrophages and the resulting susceptibility to small colony variant formation. 102,147 Another sinusoid-based approach relies on using micropillars and surface tension to create channels of cells suspended in an extracellular matrix gel. 142,148 These pillars are spaced such that when a cell-laden gel is injected, surface tension traps the gel in between the pillars.…”

Section: Sinusoid On a Chipmentioning

confidence: 99%

Opportunities and considerations for studying liver disease with microphysiological systems on a chip

Otumala,

Hellen,

Luna

et al. 2023

Lab Chip

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“…Previous studies have highlighted the insufficient ability of MΦs to effectively eliminate MRSA intracellularly, posing a significant challenge in MRSA treatment. − , Some investigations have aimed to enhance intracellular MRSA clearance by modifying MΦ polarization toward the M1 phenotype. , Additionally, there have been reports suggesting the effective clearance of MRSA by modifying MΦs in vitro and subsequently reintroducing them into the body. , However, these strategies primarily emphasize enhancing the MΦ clearance against intracellular pathogens without MRSA specificity. Addressing the efficient and specific eradication of MRSA throughout the body remains a formidable task.…”

mentioning

confidence: 99%

“…Previous studies have highlighted the insufficient ability of MΦs to effectively eliminate MRSA intracellularly, posing a significant challenge in MRSA treatment. [19][20][21]35 Some investigations have aimed to enhance intracellular MRSA clearance by modifying MΦ polarization toward the M1 phenotype. 36,37 Additionally, there have been reports suggesting the effective clearance of MRSA by modifying MΦs in vitro and subsequently reintroducing them into the body.…”

mentioning

confidence: 99%

mRNA-Laden Lipid-Nanoparticle-Enabled in Situ CAR-Macrophage Engineering for the Eradication of Multidrug-Resistant Bacteria in a Sepsis Mouse Model

Tang,

Jing,

Han

et al. 2024

ACS Nano

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Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsisassociated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ, yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the "superbug" MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.

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Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based infection model

Cited by 18 publications

References 68 publications

Natural Isoforms of Listeria monocytogenes Virulence Factor Inlb Differ in c-Met Binding Efficiency and Differently Affect Uptake and Survival Listeria in Macrophage

Natural Isoforms of Listeria monocytogenes Virulence Factor Inlb Differ in c-Met Binding Efficiency and Differently Affect Uptake and Survival Listeria in Macrophage

Opportunities and considerations for studying liver disease with microphysiological systems on a chip

mRNA-Laden Lipid-Nanoparticle-Enabled in Situ CAR-Macrophage Engineering for the Eradication of Multidrug-Resistant Bacteria in a Sepsis Mouse Model

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