scholarly journals Guanylate-Binding Protein-Dependent Noncanonical Inflammasome Activation Prevents Burkholderia thailandensis-Induced Multinucleated Giant Cell Formation

mBio ◽  
2021 ◽  
Author(s):  
Marisa Dilucca ◽  
Saray Ramos ◽  
Kateryna Shkarina ◽  
José Carlos Santos ◽  
Petr Broz

The Gram-negative bacteria of the Burkholderia species are associated with human diseases ranging from pneumonia to life-threatening melioidosis. Upon infection through inhalation, ingestion, or the percutaneous route, these bacteria can spread and establish granuloma-like lesions resulting from the fusion of host cells to form multinucleated giant cells (MNGCs). Burkholderia resistance to several antibiotics highlights the importance to better understand how the innate immune system controls infections.

2015 ◽  
Vol 41 (5) ◽  
pp. e212-e222 ◽  
Author(s):  
Mike Barbeck ◽  
Samuel Udeabor ◽  
Jonas Lorenz ◽  
Markus Schlee ◽  
Marzellus Grosse Holthaus ◽  
...  

The present preclinical and clinical study assessed the inflammatory response to a high-temperature–treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the material was well integrated into both species without any adverse reactions. Material-induced multinucleated giant cells were observed in both species and were associated with enhanced vascularization. These results revealed the high heat treatment led to an increase in the inflammatory tissue response to the biomaterial, and a combined increase in multinucleated giant cell formation. Further clarification of the differentiation of the multinucleated giant cells toward so-called osteoclast-like cells or foreign-body giant cells is needed to relate these cells to the physicochemical composition of the material.


2000 ◽  
Vol 11 (9) ◽  
pp. 3169-3176 ◽  
Author(s):  
Simonetta Falzoni ◽  
Paola Chiozzi ◽  
Davide Ferrari ◽  
Gary Buell ◽  
Francesco Di Virgilio

Cell fusion is a central phenomenon during the immune response that leads to formation of large elements called multinucleated giant cells (MGCs) of common occurrence at sites of granulomatous inflammation. We have previously reported on the involvement in this event of a novel receptor expressed to high level by mononuclear phagocytes, the purinergic P2X7receptor. Herein, we show that blockade of this receptor by a specific monoclonal antibody prevents fusion in vitro. In contrast, cell fusion is stimulated by addition of enzymes that destroy extracellular ATP (i.e., apyrase or hexokinase). Experiments performed with phagocytes selected for high (P2X7hyper) or low (P2X7hypo) P2X7expression show that fusion only occurs between P2X7hyper/P2X7hyper and not between P2X7hyper/P2X7hypo or P2X7hypo/P2X7hypo. During MGCs formation we detected activation of caspase 3, an enzyme that is powerfully stimulated by P2X7. Finally, we observed that during MGCs formation, the P2X7receptor is preferentially localized at sites of cell-to-cell contact. These findings support the hypothesis originally put forward by our group that the P2X7receptor participates in multinucleated giant cell formation.


Author(s):  
Jacob L. Stockton ◽  
Alfredo G. Torres

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei; detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outlining the concerted events in pathogenesis that lead to MNGC formation, discussing the factors that influence MNGC formation and how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.


2020 ◽  
Vol 8 (11) ◽  
pp. 1637
Author(s):  
Jacob L. Stockton ◽  
Alfredo G. Torres

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei and detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, potentially leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outline the concerted events in pathogenesis that lead to MNGC formation, discuss the factors that influence MNGC formation, and consider how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.


Author(s):  
Samar Khan

This review is intended to provide insight into the current state of understanding regarding the molecular and cellular mechanisms underlying the formation and function of various types of multinucleated giant cells. Present article mainly focus on various factors such as e.g. GCP/F, GM-CSF, Meltrin, MIP-1 that contribute to giant cell formation and function. This review focuses on recent efforts to develop a better understanding of the molecular and cellular biology of multinucleated giant cell formation and function.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Lixiang Chen ◽  
Xue Liu ◽  
Xin Yu ◽  
Rongrong Ren ◽  
Chao Wang ◽  
...  

Chlamydiae are Gram-negative bacteria, which replicate exclusively in the infected host cells. Infection of the host cells by Chlamydiae stimulates the innate immune system leading to an inflammatory response, which is manifested not only by secretion of proinflammatory cytokines such as IL-1βfrom monocytes, macrophages, and dendritic cells, but also possibly by cell death mediated by Caspase-1 pyroptosis. RIP3 is a molecular switch that determines the development of necrosis or inflammation. However, the involvement of RIP3 in inflammasome activation byChlamydia muridaruminfection has not been clarified. Here, we assessed the role of RIP3 in synergy with Caspase-1 in the induction of IL-1βproduction in BMDM after either LPS/ATP orChlamydia muridarumstimulation. The possibility of pyroptosis and necroptosis interplays and the role of RIP3 in IL-1βproduction duringChlamydia muridaruminfection in BMDM was investigated as well. The data indicated that RIP3 is involved in NLRP3 inflammasome activation in LPS/ATP-stimulated BMDMs but not inChlamydia muridaruminfection. Pyroptosis occurred in BMDM after LPS/ATP stimulation orChlamydia muridaruminfection. Moreover, the results also illuminated the important role of the Caspase-1-mediated pyroptosis process which does not involve RIP3. Taken together, these observations may help shed new light on details in inflammatory signaling pathways activated byChlamydia muridaruminfection.


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