Extracellular Vesicles from <i>Pseudomonas aeruginosa</i> Suppress MHC-Related Molecules in Human Lung Macrophages

Armstrong, David A.; Lee, Min Kyung; Hazlett, Haley F.; Dessaint, John A.; Mellinger, Diane; Aridgides, Daniel; Hendricks, Gregory M.; Abdalla, Moemen; Christensen, Brock C.; Ashare, Alix

doi:10.4049/immunohorizons.2000026

Cited by 25 publications

(20 citation statements)

References 59 publications

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“…Several mechanisms have been identified including alteration and/or activation of redundant signaling pathways, and downmodulation of the antigen-presenting machinery to evade anti-tumor-specific T cells, all contributing to the resurgence of resistant tumor cells 1 , 4 . In a recent study, TGFβ has been identified as a major player in driving a resistant phenotype and contributing to MHC class I downmodulation in melanoma 35 . We and others have shown that tumor-infiltrating fibroblasts, macrophages, and B-cells have an important role in therapy resistance 2 , 36 , 37 .…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy

et al. 2021

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Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3+ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8+/Granz B+ T cells homeostasis are observed in tumor regions where FOXP3+ Treg and mast cells co-localize, with such features associated with resistance to anti-PD-1 treatment. Combining anti-PD-1 with sunitinib or imatinib results in the depletion of mast cells and complete regression of tumors. Our results thus implicate mast cell depletion for improving the efficacy of anti-PD-1 therapy.

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Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy

et al. 2021

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“…A last important point has to be mentioned: cell 1 in Figure 6 A and cell 3 in Figure 7 H were surrounded by material that likely corresponds to excreted vesicles. Such vesicles are the sign of a stressed or not-healthy bacterium [ 49 , 50 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Impact of Growth Conditions on Pseudomonas fluorescens Morphology Characterized by Atomic Force Microscopy

Kahli

Béven

Grauby–Heywang

et al. 2022

IJMS

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This work is dedicated to the characterization by Atomic Force Microscopy (AFM) of Pseudomonas fluorescens, bacteria having high potential in biotechnology. They were first studied first in optimal conditions in terms of culture medium and temperature. AFM revealed a more-or-less elongated morphology with typical dimensions in the micrometer range, and an organization of the outer membrane characterized by the presence of long and randomly distributed ripples, which are likely related to the organization of lipopolysaccharides (LPS). The outer membrane also presents invaginations, some of them showing a reorganization of ripples, which could be the first sign of a bacterial stress response. In a second step, bacteria grown under unfavorable conditions were characterized. The choice of the medium appeared to be more critical in the case of the second generation of cells, the less adapted medium inducing not only changes in the membrane organization but also larger damages in bacteria. An increased growth temperature affected both the usual “swollen” morphology and the organization of the outer membrane. Here also, LPS likely contribute to membrane remodelling, which makes them potential markers to track cell state changes.

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“…EVs secreted by P. aeruginosa (also known as outer membrane vesicles (OMVs) contain virulence factors, such as peptides, which contribute to biofilm formation, protecting growing bacteria from the host immune response and antibiotic action (Esoda and Kuehn, 2019). Additionally, P. aeruginosa-released EVs downregulate the expression of MHCrelated molecules in pulmonary macrophages, reducing pathogen clearance (Armstrong et al, 2020). Also, EVs released by P. aeruginosa-infected microglia cells diminish cell viability and the expression of the CC-chemokine ligand CCL4 by uninfected microglia cells (Jones et al, 2019).…”

Section: Extracellular Vesicles As Pivotal Players In Biological Processes Extracellular Vesicles In Invader-host Interplay: Prominent Prmentioning

confidence: 99%

Extracellular Vesicles: Potential Role in Remote Signaling and Inflammation in Trypanosoma cruzi-Triggered Disease

Dantas-Pereira¹,

Menna-Barreto²,

Lannes-Vieira³

2021

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs) act as cell communicators and immune response modulators and may be employed as disease biomarkers and drug delivery systems. In infectious diseases, EVs can be released by the pathogen itself or by the host cells (infected or uninfected), potentially impacting the outcome of the immune response and pathological processes. Chagas disease (CD) is caused by infection by the protozoan Trypanosoma cruzi and is the main cause of heart failure in endemic areas. This illness attracted worldwide attention due to the presence of symptomatic seropositive subjects in North America, Asia, Oceania, and Europe. In the acute phase of infection, nonspecific signs, and symptoms contribute to miss diagnosis and early etiological treatment. In this phase, the immune response is crucial for parasite control; however, parasite persistence, dysregulated immune response, and intrinsic tissue factors may contribute to the pathogenesis of chronic CD. Most seropositive subjects remain in the indeterminate chronic form, and from 30 to 40% of the subjects develop cardiac, digestive, or cardio-digestive manifestations. Identification of EVs containing T. cruzi antigens suggests that these vesicles may target host cells and regulate cellular processes and the immune response by molecular mechanisms that remain to be determined. Parasite-released EVs modulate the host-parasite interplay, stimulate intracellular parasite differentiation and survival, and promote a regulatory cytokine profile in experimental models of CD. EVs derived from the parasite-cell interaction inhibit complement-mediated parasite lysis, allowing evasion. EVs released by T. cruzi-infected cells also regulate surrounding cells, maintaining a proinflammatory profile. After a brief review of the basic features of EVs, the present study focuses on potential participation of T. cruzi-secreted EVs in cell infection and persistence of low-grade parasite load in the chronic phase of infection. We also discuss the role of EVs in shaping the host immune response and in pathogenesis and progression of CD.

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Extracellular Vesicles from Pseudomonas aeruginosa Suppress MHC-Related Molecules in Human Lung Macrophages

Cited by 25 publications

References 59 publications

Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy

Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy

Impact of Growth Conditions on Pseudomonas fluorescens Morphology Characterized by Atomic Force Microscopy

Extracellular Vesicles: Potential Role in Remote Signaling and Inflammation in Trypanosoma cruzi-Triggered Disease

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