Mechanisms of phagocytosis and host clearance of<i>Pseudomonas aeruginosa</i>

Lovewell, Rustin R.; Patankar, Yash R.; Berwin, Brent

doi:10.1152/ajplung.00335.2013

Cited by 145 publications

(140 citation statements)

References 154 publications

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“…Neutrophils are prominent phagocytes during P. aeruginosa pneumonia. This is demonstrated by increased mortality due to bacterial overgrowth in P. aeruginosainfected mice when neutrophils are depleted (8,30,31). In our model, Chil1-deficient mice recruited more neutrophils during P. aeruginosa infection than WT mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia

et al. 2016

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dPseudomonas aeruginosa causes hospital-acquired pneumonia and is associated with high mortality. An effective response to such an infection includes efficient clearance of pathogenic organisms while limiting collateral damage from the host inflammatory response, known as host resistance and host tolerance, respectively. P. aeruginosa expresses a type III secretion system (T3SS) needle complex that induces NLRC4 (NOD-like receptor C4) activation, interleukin-1␤ (IL-1␤) production, and host tissue damage. Chitinase 3-like-1 (Chil1) is expressed during infection and binds to its receptor, IL-13 receptor ␣2 (IL-13R␣2), to regulate the pathogen-host response during Streptococcus pneumoniae infection, but the role Chil1 plays in balancing the host resistance and host tolerance during P. aeruginosa pneumonia is not known. We conducted experiments using C57BL/6 mice with or without a genetic deficiency of Chil1 and demonstrated that Chil1-deficient mice succumb to P. aeruginosa infection more rapidly than the wild type (WT). The decreased survival time in infected Chil1-deficient mice is associated with more neutrophils recruited to the airways, more lung parenchymal damage, and increased pulmonary consolidation while maintaining equivalent bacterial killing compared to WT mice. Infected Chil1-deficient mice and bone marrow-derived macrophages (BMDMs) from Chil1-deficient mice have increased production of tumor necrosis factor alpha (TNF-␣) and IL-1␤ compared to infected WT mice and macrophages. Infection of Chil1-deficient BMDMs with non-NLRC4-triggering P. aeruginosa, which is deficient in the T3SS needle complex, did not alter the excessive IL-1␤ production compared to BMDMs from WT mice. The addition of recombinant Chil1 decreases the excessive IL-1␤ production but only partially rescues stimulated BMDMs from IL-13R␣2-deficient mice. Our data provide mechanistic insights into how Chil1 regulates P. aeruginosa-induced host responses. Hospital-acquired pneumonia is a common cause of hospitalassociated death and morbidity (1, 2). Pseudomonas aeruginosa causes both acute and chronic respiratory infections. P. aeruginosa is a common cause of opportunistic infection in hospitalized patients and is known to chronically colonize patients with structural lung diseases, such as cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease (COPD), as opposed to nonstructural lung diseases, such as pulmonary edema, chronic thrombotic disease, or atelectasis (3, 4). Acute lower respiratory tract infections caused by P. aeruginosa can lead to severe complications, such as acute respiratory distress syndrome (ARDS) and sepsis (5, 6). The clinical outcomes associated with P. aeruginosa pneumonia are the product of the immune system's ability to recognize and clear pathogenic organisms, known as host resistance (7-9). Recent investigations have led to a better appreciation that the pathogen-mediated immune response also causes collateral damage to host tissues independently of the bacterial burden, which also can contr...

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Section: Resultsmentioning

confidence: 99%

Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia

et al. 2016

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“…The inflammatory response towards acute P. aeruginosa pneumonia is chiefly governed by expression of proinflammatory cytokines including TNFα, IFNγ, IL-1α, IL-1β and IL-12 as well as chemotactic molecules such as IL-8 secreted by innate immune cells, epithelial cells and alveolar macrophages that result in neutrophil recruitment to the site of infection (54)(55)(56)(57). However, the choice of inoculum dose is of high importance because a relatively high dose of P. aeruginosa causes a more marked increase in production of cytokines in the early time-points compared to lower doses (50) and thus has important consequences for studying pneumonia development.…”

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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“…How P. aeruginosa avoids the innate immune system to survive in the bloodstream and disseminate to various organs is not well understood. In vitro, P. aeruginosa has the capacity to evade complement deposition, prevent neutrophil recruitment, and even have cytolytic effects on immune cells upon phagocytosis (7). However, which of these evasion or subversion mechanisms might work in vivo remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature

Thanabalasuriar

Surewaard

Willson

et al. 2017

Journal of Clinical Investigation

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Mechanisms of phagocytosis and host clearance ofPseudomonas aeruginosa

Cited by 145 publications

References 154 publications

Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia

Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia

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

Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature

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