Therapeutic stem cell‐derived alveolar‐like macrophages display bactericidal effects and resolve <i>Pseudomonas aeruginosa</i>‐induced lung injury

Bouch, Sheena; Litvack, Michael; Litman, Kymberly; Luo, Lisha; Post, Alex; Williston, Emma; Park, Amber J.; Roach, Elyse J.; Berezuk, Alison; Khursigara, Cezar M.; Post, Martin

doi:10.1111/jcmm.17324

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…Alveolar macrophages (AMs) are the first phagocytic cells that encounter invaded pathogens and efficiently clear the pathogens by secreting complement factors, reactive oxygen species, and inflammatory cytokines [ 66 ]. Also, these AMs play a critical role in resolving lung injury [ 67 ]. P .…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction

Kumar,

Pestrak,

et al. 2023

PLoS Pathog

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Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust inflammatory response, which ideally enhances bacterial clearance. Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how P.a. lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that P.a. infection of the lungs led to severe cardiac left ventricular dysfunction and electrical abnormalities. More specifically, we found that neutrophil recruitment and release of S100A8/A9 in the lungs activates the TLR4/RAGE signaling pathways, which in turn enhance systemic inflammation and subsequent cardiac dysfunction. Paradoxically, global deletion of S100A8/A9 did not improve but aggravated cardiac dysfunction and mortality likely due to uncontrolled bacterial burden in the lungs and heart. Our results indicate that P.a. infection induced release of S100A8/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting P.a. growth.

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Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction

Kumar,

Pestrak,

et al. 2023

PLoS Pathog

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“…However, stem cells still face many challenges in the treatment of infectious diseases associated with S. aureus : (1) Complexity of Mechanisms: The intricacies of stem cell therapy in combating infections surpass those of conventional antibiotic therapy. Stem cells exhibit a diverse range of mechanisms including direct antimicrobial activity, immune response modulation, and tissue repair following infection-induced damage [ 117 , 118 ]. The multifaceted nature of these mechanisms presents obstacles for both research and practical implementation in clinical settings.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Effects of Staphylococcus aureus on stem cells and potential targeted treatment of inflammatory disorders

Liu,

Lin

et al. 2024

Stem Cell Res Ther

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Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.

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“…The lungs are one of the most susceptible organs to bacteria, and bacterial lung infections result in more than 4 million deaths worldwide every year, and with the emerging antibiotic resistance it necessitates the development of novel therapeutic approaches [ 54 ]. Great efforts have been made to evaluate the therapeutic efficacy of GSNO in pulmonary infections [ 40 , [45] , [46] , [47] ].…”

Section: Antibacterial Property Of Gsno and Associated Mechanismsmentioning

confidence: 99%

Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials

Hu¹,

Ye²,

Pi³

et al. 2022

Materials Today Bio

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Therapeutic stem cell‐derived alveolar‐like macrophages display bactericidal effects and resolve Pseudomonas aeruginosa‐induced lung injury

Cited by 5 publications

References 42 publications

Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction

Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction

Effects of Staphylococcus aureus on stem cells and potential targeted treatment of inflammatory disorders

Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials

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