Lung defense against Pseudomonas aeruginosa: the recognition by host cells of either LPS or flagellin is necessary and sufficient

Raoust, Eloïse; Balloy, Viviane; García-Verdugo, Ignacio; Touqui, Lhousseine; Ramphal, Reuben; Chignard, Michel

doi:10.1016/s1569-1993(09)60207-1

Cited by 3 publications

(3 citation statements)

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“…42 The conserved domains of flagellin also serve as a pathogen-associated molecular pattern that is capable of inducing strong inflammatory responses via engagement of TLR5. 43 Additionally, the outer membrane proteins OprE and OprM were enriched by 3.1-fold and 4.5-fold, respectively.…”

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confidence: 96%

Multiantigenic Nanotoxoids for Antivirulence Vaccination against Antibiotic-Resistant Gram-Negative Bacteria

et al. 2019

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Infections caused by multidrug-resistant gram-negative bacteria have emerged as a major threat to public health worldwide. The high mortality and prevalence, along with the slow pace of new antibiotic discovery, highlight the necessity for new disease management paradigms. Here, we report on the development of a multiantigenic nanotoxoid vaccine based on macrophage membrane-coated nanoparticles for eliciting potent immunity against pathogenic Pseudomonas aeruginosa. The design of this biomimetic nanovaccine leverages the specific role of macrophages in clearing pathogens and their natural affinity for various virulence factors secreted by the bacteria. It is demonstrated that the macrophage nanotoxoid is able to display a wide range of P. aeruginosa antigens, and the safety of the formulation is confirmed both in vitro and in vivo. When used to vaccinate mice via different administration routes, the nanotoxoid is capable of eliciting strong humoral immune responses that translate into enhanced protection against live bacterial infection in a pneumonia model. Overall, the work presented here provides new insights into the design of safe, multiantigenic antivirulence vaccines using biomimetic nanotechnology and the application of these nanovaccines towards the prevention of difficult-to-treat gram-negative infections.

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confidence: 96%

Multiantigenic Nanotoxoids for Antivirulence Vaccination against Antibiotic-Resistant Gram-Negative Bacteria

et al. 2019

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“…C57/Bl6 mice lung epithelial cells preparation was as described in Raoust et al (22). For FACS analysis, cells (from lung extracts, BALs, isolated AMs or BMDMs) were first incubated (10 min, 4°C) with a cocktail of a viability dye and Fc Block antibody.…”

Section: D-flow Cytometry Analysismentioning

confidence: 99%

Use of IL-6-elafin genetically modified regulatory macrophages as an immunotherapy against acute Pseudomonas aeruginosa infection in the lung

Kheir

Villeret

García-Verdugo

et al. 2021

Revue des Maladies Respiratoires

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“…In contrast, AM responses to bacterial infections are more varied. AMs infected ex vivo with Pseudomonas aeruginosa produce TNF and IL-6 13 , as well as IL-1β following inflammasome activation 14 . Additionally, depletion of AMs in vivo prior to P. aeruginosa infection reduces neutrophil recruitment 15 .…”

Section: Introductionmentioning

confidence: 99%

Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages

Lim,

Cervantes,

Pham

et al. 2024

Preprint

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Alveolar macrophages (AMs) are lower-airway resident myeloid cells and are among the first to respond to inhaled pathogens. Here, we interrogate AM innate sensing to Pathogen Associated Molecular Patterns (PAMPs) and determine AMs have decreased responses to low-dose LPS compared to other macrophages, as measured by TNF, IL-6,Ifnb, andIfit3. We find the reduced response to low-dose LPS correlates with minimal TLR4 and CD14 surface expression, despite sufficient internal expression of TLR4. Additionally, we find that AMs do not produce IL-10 in response to a variety of PAMPs due to low expression of transcription factor c-Maf and that lack of IL-10 production contributes to an enhancement of pro-inflammatory responses by Type I IFN. Our findings demonstrate that AMs have cell-intrinsic dampened responses to LPS, which is enhanced by type I IFN exposure. These data implicate conditions where AMs may have reduced or enhanced sentinel responses to bacterial infections.

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Lung defense against Pseudomonas aeruginosa: the recognition by host cells of either LPS or flagellin is necessary and sufficient

Cited by 3 publications

References 0 publications

Multiantigenic Nanotoxoids for Antivirulence Vaccination against Antibiotic-Resistant Gram-Negative Bacteria

Multiantigenic Nanotoxoids for Antivirulence Vaccination against Antibiotic-Resistant Gram-Negative Bacteria

Use of IL-6-elafin genetically modified regulatory macrophages as an immunotherapy against acute Pseudomonas aeruginosa infection in the lung

Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages

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