Rescue from Pseudomonas aeruginosa Airway Infection via Stem Cell Transplantation

Brinkert, Kerstin; Hedtfeld, Silke; Burhop, Annina; Gastmeier, Rena; Gad, Pauline; Wedekind, Dirk; Kloth, Christina; Rothschuh, Justin; Lachmann, Nico; Hetzel, Miriam; Jirmo, Adan Chari; López-Rodríguez, Elena; Brandenberger, Christina; Hansen, Gesine; Schambach, Axel; Ackermann, Mania; Tümmler, Burkhard; Munder, Antje

doi:10.1016/j.ymthe.2020.12.003

Cited by 9 publications

(13 citation statements)

References 72 publications

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“…A .‐induced pneumonia. 37 , 38 , 39 At Day 7, administration of ALMs mitigated P . A .‐induced structural lung injury, namely epithelial thickening, sloughing and infiltration (Figure 7B ).…”

Section: Discussionmentioning

confidence: 98%

“…A .‐induced lung injury, and further supports the concept of ALMs promoting airway repair in disease models. 17 Recently, it has been reported that murine hematopoietic stem cell transplantation 39 or delivery of human iPSC‐derived macrophages 32 rescued mice from P . A .…”

Section: Discussionmentioning

confidence: 99%

“…Together, these data are the first to show ALM-driven resolution of P.A.-induced lung injury, and further supports the concept of ALMs promoting airway repair in disease models. 17 Recently, it has been reported that murine hematopoietic stem cell transplantation 39 or delivery of human iPSC-derived macrophages 32 rescued mice from P.A. airway infection; however, the critical distinction is that these graft-derived or instilled macrophages were of bone marrow or non-primitive origins, unlike ALMs that are engineered to reside in the lung for long periods of time.…”

Section: Surface Expression Of Known 1'am Markersmentioning

confidence: 99%

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

Bouch

Litvack

Litman

et al. 2022

J Cellular Molecular Medi

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Communicable bacterial lung infections affect hundreds of millions of individuals, with respiratory infections being the leading cause of death in developing countries accounting for greater than 4 million deaths per year. 1 Common bacterial infections and diseases include pneumonia, tuberculosis and pertussis; however, patients with compromised lung immunity, such as individuals with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD) and lung transplant recipients, are particularly

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Surface Expression Of Known 1'am Markersmentioning

confidence: 99%

See 1 more Smart Citation

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

Bouch

Litvack

Litman

et al. 2022

J Cellular Molecular Medi

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“…However, as chronic airway infections also represent one of the main causes of morbidity and mortality in CF patients, recent studies investigated the impact of CFTR mutations on the functionality of AM. Indeed, alveolar macrophages from murine cftr −/− models, show reduced phagosome acidification and bactericidal activity [78,115].…”

Section: The Role Of Am In Infections Of the Lower Respiratory Tractmentioning

confidence: 99%

“…It is wellknown that irradiation and chemotherapy preconditioning before HSCT are also depleting the pulmonary AM niche, which can then be repopulated by donor-derived monocytes. An allogeneic HSCT approach transplanting healthy HSC into cystic fibrosis (CF) mice recently demonstrated prevention of pulmonary P. aeruginosa infection by replacing malfunctioning AM [78]. By combining autologous HSCT with gene therapy, we previously demonstrated protection against pulmonary BCG infection in Ifnγr1-deficient MSMD mice [79].…”

Section: Therapeutic Approaches To Treat Pulmonary Infectionsmentioning

confidence: 99%

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Hetzel

Ackermann

Lachmann

2021

IJMS

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Macrophages act as immune scavengers and are important cell types in the homeostasis of various tissues. Given the multiple roles of macrophages, these cells can also be found as tissue resident macrophages tightly integrated into a variety of tissues in which they fulfill crucial and organ-specific functions. The lung harbors at least two macrophage populations: interstitial and alveolar macrophages, which occupy different niches and functions. In this review, we provide the latest insights into the multiple roles of alveolar macrophages while unraveling the distinct factors which can influence the ontogeny and function of these cells. Furthermore, we will highlight pulmonary diseases, which are associated with dysfunctional macrophages, concentrating on congenital diseases as well as pulmonary infections and impairment of immunological pathways. Moreover, we will provide an overview about different treatment approaches targeting macrophage dysfunction. Improved knowledge of the role of macrophages in the onset of pulmonary diseases may provide the basis for new pharmacological and/or cell-based immunotherapies and will extend our understanding to other macrophage-related disorders.

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IL-6-elafin genetically modified macrophages as a lung immunotherapeutic strategy against Pseudomonas aeruginosa infections

et al. 2022

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Pseudomonas aeruginosa (P.a) infections are a major public health issue in ventilator-associated pneumoniae, cystic fibrosis, and chronic obstructive pulmonary disease exacerbations. P.a is multidrug resistant, and there is an urgent need to develop new therapeutic approaches. Here, we evaluated the effect of direct pulmonary transplantation of gene-modified (elafin and interleukin [IL]-6) syngeneic macrophages in a mouse model of acute P.a infection. Wild-type (WT) or Elafin-transgenic (eTg) alveolar macrophages (AMs) or bone marrow-derived macrophages (BMDMs) were recovered from bronchoalveolar lavage or generated from WT or eTg mouse bone marrow. Cells were modified with adenovirus IL-6 (Ad-IL-6), characterized in vitro, and transferred by oropharyngeal instillation in the lungs of naive mice. The protective effect was assessed during P.a acute infection (survival studies, mechanistic studies of the inflammatory response). We show that a single bolus of genetically modified syngeneic AMs or BMDMs provided protection in our P.ainduced model. Mechanistically, Elafin-modified AMs had an IL-6-IL-10-IL-4R-IL-22-antimicrobial molecular signature that, in synergy with IL-6, enhanced epithelial cell proliferation and tissue repair in the alveolar unit. We believe that this innovative cell therapy strategy could be of value in acute bacterial infections in the lung.

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Rescue from Pseudomonas aeruginosa Airway Infection via Stem Cell Transplantation

Cited by 9 publications

References 72 publications

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

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

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

IL-6-elafin genetically modified macrophages as a lung immunotherapeutic strategy against Pseudomonas aeruginosa infections

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