Protection against Pseudomonas aeruginosa lung infection in mice by recombinant OprF-pulsed dendritic cell immunization

Peluso, Lucia; Luca, Antonella De; Bozza, Silvia; Leonardi, Antonio; Giovannini, Gloria; Lavorgna, Alfonso; Rosa, Gaetano De; Mascolo, Massimo; Luna, Loredana Ortega De; Catania, Maria Rosaria; Romani, Luigina; Rossano, Fabio

doi:10.1186/1471-2180-10-9

Cited by 30 publications

(22 citation statements)

References 39 publications

(41 reference statements)

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“…The mouse model of P. aeruginosa lung infection was adapted from previously published protocols (37). Bacteria were grown at room temperature up to an OD 600 of 0.5 and were then collected by centrifugation, washed once in PBS, and resuspended again in PBS.…”

Section: Methodsmentioning

confidence: 99%

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Pseudomonas aeruginosa Condensins Support Opposite Differentiation States

et al. 2016

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Condensins play a key role in global chromosome packing. Pseudomonas aeruginosa encodes two condensins, SMC-ScpAB and MksBEF. We report here that the two proteins are involved in the differentiation of the bacterium and impose opposite physiological states. The inactivation of SMC induced a state characterized by increased adhesion to surfaces as well as defects in competitive growth and colony formation. In contrast, MksB-deficient cells were impaired in biofilm formation with no obvious defects during planktonic growth. The phenotype of the double mutant was dominated by the absence of MksB, indicating that the observed growth defects are regulatory in their nature rather than structural. ATPase mutations recapitulated many of the phenotypes of the condensins, indicating their requirement for a functional protein. Additionally, inactivation of condensins dramatically reduced the virulence of the bacterium in a murine model of lung infection. These data demonstrate that condensins are involved in the differentiation of P. aeruginosa and reveal their importance for pathogenicity. IMPORTANCEAdaptation and differentiation play key roles in bacterial pathogenicity. In Pseudomonas aeruginosa, an opportunistic human pathogen, these processes are mediated by the activity of an intricate regulatory network. We describe here novel members of this network, condensins. We show that the two P. aeruginosa condensins specialize in the establishment of the sessile and planktonic states of the bacterium. Whereas condensins have well-established roles in global chromosome organization, their roles in regulating bacterial physiology have remained unknown. Our data indicate that the two programs may be linked. We further show that condensins are essential for the pathogenicity of P. aeruginosa.

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Section: Methodsmentioning

confidence: 99%

“…Even though the phenotype of condensin mutations appeared rather mild, their effect on epigenetic states was quite dramatic. To determine whether or not these changes alter the virulence of P. aeruginosa, we evaluated ⌬smc and ⌬smc ⌬mksB strains in a mouse model of lung infection (37).…”

Section: Smc and Mksb Are Expendable And Antagonistic To Each Othermentioning

confidence: 99%

Pseudomonas aeruginosa Condensins Support Opposite Differentiation States

et al. 2016

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“…Intratracheal instillation is the most used method in HAP research and involves injecting the bacterial suspension directly into the trachea or lungs followed by air for dispersion of the bolus (33,(43)(44)(45)(46)(47)(48)(49)(50). This method gives the most precise control on the delivered dose.…”

Section: Types Of Pneumonia Modelsmentioning

confidence: 99%

Animal models of hospital-acquired pneumonia: current practices and future perspectives

Bielen¹,

Jongers²,

Malhotra-Kumar³

et al. 2017

Ann. Transl. Med.

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Lower respiratory tract infections are amongst the leading causes of mortality and morbidity worldwide. Especially in hospital settings and more particularly in critically ill ventilated patients, nosocomial pneumonia is one of the most serious infectious complications frequently caused by opportunistic pathogens.Pseudomonas aeruginosa is one of the most important causes of ventilator-associated pneumonia as well as the major cause of chronic pneumonia in cystic fibrosis patients. Animal models of pneumonia allow us to investigate distinct types of pneumonia at various disease stages, studies that are not possible in patients.Different animal models of pneumonia such as one-hit acute pneumonia models, ventilator-associated pneumonia models and biofilm pneumonia models associated with cystic fibrosis have been extensively studied and have considerably aided our understanding of disease pathogenesis and testing and developing new treatment strategies. The present review aims to guide investigators in choosing appropriate animal pneumonia models by describing and comparing the relevant characteristics of each model using P. aeruginosa as a model etiology for hospital-acquired pneumonia. Key to establishing and studying these animal models of infection are well-defined end-points that allow precise monitoring and characterization of disease development that could ultimately aid in translating these findings to patient populations in order to guide therapy. In this respect, and discussed here, is the development of humanized animal models of bacterial pneumonia that could offer unique advantages to study bacterial virulence factor expression and host cytokine production for translational purposes.

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“…OprF has intrinsic ability to stimulate release of diverse innate cytokines from dendritic cells (43); although this clearly would not have contributed to the differences in epitope focus we observed in peptide-specific CD4 responses, it may be that in chronically PA-infected patients showing up-regulated OprF, this upregulation may stimulate increased systemic IL-12 and tumor necrosis factor-a. From our study we cannot be certain whether the altered T-cell response pattern we observed is cause or effect of a heightened susceptibility to PA infection.…”

Section: Original Article Discussionmentioning

confidence: 63%

Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F

Quigley

Reynolds

Goudet

et al. 2015

Am J Respir Crit Care Med

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Rationale: Pseudomonas aeruginosa (PA) is an environmental pathogen that commonly infects individuals with cystic fibrosis (CF) and non-CF bronchiectasis, impacting morbidity and mortality. To understand the pathobiology of interactions between the bacterium and host adaptive immunity and to inform rational vaccine design, it is important to understand the adaptive immune correlates of disease.Objectives: To characterize T-cell immunity to the PA antigen outer membrane porin F (OprF) by analyzing immunodominant epitopes in relation to infection status.Methods: Patients with non-CF bronchiectasis were stratified by frequency of PA isolation. T-cell IFN-g immunity to OprF and its immunodominant epitopes was characterized. Patterns of human leukocyte antigen (HLA) restriction of immunodominant epitopes were defined using HLA class II transgenic mice. Immunity was characterized with respect to cytokine and chemokine secretion, antibody response, and T-cell activation transcripts. Measurements and Main Results:Patients were stratified according to whether PA was never, sometimes (,50%), or frequently (>50%) isolated from sputum. Patients with frequent PA sputumpositive isolates were more likely to be infected by mucoid PA, and they showed a narrow T-cell epitope response and a relative reduction in Th1 polarizing transcription factors but enhanced immunity with respect to antibody production, innate cytokines, and chemokines. Conclusions:We have defined the immunodominant, HLArestricted T-cell epitopes of OprF. Our observation that chronic infection is associated with a response of narrowed specificity, despite strong innate and antibody immunity, may help to explain susceptibility in these individuals and pave the way for better vaccine design to achieve protective immunity.

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Protection against Pseudomonas aeruginosa lung infection in mice by recombinant OprF-pulsed dendritic cell immunization

Cited by 30 publications

References 39 publications

Pseudomonas aeruginosa Condensins Support Opposite Differentiation States

Pseudomonas aeruginosa Condensins Support Opposite Differentiation States

Animal models of hospital-acquired pneumonia: current practices and future perspectives

Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F

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