Pretreatment with cathelicidin-BF ameliorates Pseudomonas aeruginosa pneumonia in mice by enhancing NETosis and the autophagy of recruited neutrophils and macrophages

Liu, Cunbao; Qi, Jialong; Shu, Bin; Gao, Ruiyu; Gao, Feng; Xie, Hanghang; Yuan, Mingcui; Liu, Hongxian; Jin, Sun; Wu, Fei; Ma, Yanbing

doi:10.1016/j.intimp.2018.10.030

Cited by 23 publications

(22 citation statements)

References 37 publications

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“…Alveolar macrophages and neutrophils are the first immune cells in the host innate response to bacterial pathogen infection.34 Our recent work indicated that Cathelicidin-BF , another AMP subtype, enhanced neutrophil extracellular traps, which are the main facilitators of the capture and clearance of bacteria through the activation of innate immunity.35 Other studies have indicated that macrophages also contribute to the clearance of bacterial pathogen infection.36 In this study, our results demonstrated that Tachyplesin III improved alveolar macrophage phagocytosis in a dose-dependent manner in vitro (Figure 5), which may directly reduce the BALF burden (Figure 3C). Thus, our study reports a novel therapeutic strategy for gram-negative MDR bacterial coinfection using the AMP Tachyplesin III .…”

Section: Discussionmentioning

confidence: 99%

“…The lung tissue histology analysis was performed as previously described.35 Briefly, the left lung tissues were harvested from mice the day after bacterial infection and fixed in 4% paraformaldehyde at room temperature for 24 hrs. Subsequently, the tissues were embedded in paraffin and stained with a hematoxylin and eosin (H & E) kit purchased from Solarbio ® Life Science.…”

Section: Methodsmentioning

confidence: 99%

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Potential role of the antimicrobial peptide Tachyplesin III against multidrug-resistant P. aeruginosa and A. baumannii coinfection in an animal model

Qi¹,

Gao²,

Liu³

et al. 2019

IDR

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BackgroundTachyplesin III, an antimicrobial peptide (AMP), provides protection against multidrug-resistant (MDR) bacterial infections and shows cytotoxicity to mammalian cells. Mixed bacterial infections, of which P. aeruginosa plus A. baumannii is the most common and dangerous combination, are critical contributors to the morbidity and mortality of long-term in-hospital respiratory medicine patients. Therefore, the development of effective therapeutic approaches to mixed bacterial infections is urgently needed.Methods and resultsIn this study, we demonstrated that compared with individual infections, mixed infections with MDR bacteria P. aeruginosa and A. baumannii cause more serious diseases, with increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokines (MCP-1/MIP-2) and reduced mouse survival. In vitro treatment with Tachyplesin III enhanced phagocytosis in a mouse alveolar macrophage cell line (MH-S). Strikingly, in vivo, Tachyplesin III demonstrated a potential role against mixed-MDR bacterial coinfection. The bacterial burden in bronchoalveolar lavage fluid (BALF) was significantly reduced in the Tachyplesin III-treated group. In addition, a systemic reduction in pro-inflammatory cytokines and decreased lung injury occurred with Tachyplesin III therapy.ConclusionTherefore, our study demonstrated that Tachyplesin III represents a potential therapeutic treatment against mixed-MDR bacterial infection in vivo, which sheds light on the development of therapeutic strategies against mixed-MDR bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Potential role of the antimicrobial peptide Tachyplesin III against multidrug-resistant P. aeruginosa and A. baumannii coinfection in an animal model

Qi¹,

Gao²,

Liu³

et al. 2019

IDR

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“…Autophagy not only does actively participate in NET formation but also inhibits the excessive release of NETs. A study of mice infected with Pseudomonas aeruginosa and affected by pneumonia showed that the activation of innate immunity improves the disease outcome via antimicrobial agents that enhance autophagy to rapidly eliminate NETs, thus preventing severe tissue damage [132]. Enhancement of NET generation and release, which requires autophagy, is the key process in antimicrobial treatment, providing evidence of the dual role of autophagy in NETosis.…”

Section: Autophagy Immunity and Virus Infectionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

Cicco

Racanelli

et al. 2020

Mediators of Inflammation

153

148

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COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

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“…Importantly, the microspheres prevented peptide degradation while still maintaining antimicrobial efficacy against E. coli, Shigella dysenteriae, and Salmonella typhi (Bao et al, 2018). In addition, using a murine model of P. aeruginosa pneumonia, intravenous pre-treatment of formulated cathelicidin-BF activated the immune response to improve antibacterial functions while enhancing macrophage clearance and dampening inflammation via obstruction of the NF-κB signaling cascade (Liu et al, 2018). Cathelicidin-BF has also been conjugated to PLGA polymers, resulting in even slower release (up to 30 days) while exhibiting minimal toxicity toward eukaryotic cells as well as low hemolysis (Schlosser et al, 2008).…”

Section: Novel Formulations For Peptide Deliverymentioning

confidence: 99%

Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance

et al. 2020

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Host-defense peptides (HDPs) are vital components of innate immunity in all vertebrates. While their antibacterial activity toward bacterial cells was the original focus for research, their ability to modulate immune and inflammatory processes has emerged as one of their major functions in the host and as a promising approach from which to develop novel therapeutics targeting inflammation and innate immunity. In this review, with particular emphasis on the cathelicidin family of peptides, the roles of natural HDPs are examined in managing immune activation, cellular recruitment, cytokine responses, and inflammation in response to infection, as well as their contribution(s) to various inflammatory disorders and autoimmune diseases. Furthermore, we discuss current efforts to develop synthetic HDPs as therapeutics aimed at restoring balance to immune responses that are dysregulated and contribute to disease pathologies.

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Pretreatment with cathelicidin-BF ameliorates Pseudomonas aeruginosa pneumonia in mice by enhancing NETosis and the autophagy of recruited neutrophils and macrophages

Cited by 23 publications

References 37 publications

<p>Potential role of the antimicrobial peptide <em>Tachyplesin III</em> against multidrug-resistant <em>P. aeruginosa</em> and <em>A. baumannii</em> coinfection in an animal model</p>

<p>Potential role of the antimicrobial peptide <em>Tachyplesin III</em> against multidrug-resistant <em>P. aeruginosa</em> and <em>A. baumannii</em> coinfection in an animal model</p>

Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance

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