Platelets Fuel the Inflammasome Activation of Innate Immune Cells

Rolfes, Verena; Ribeiro, Lucas S.; Hawwari, Ibrahim; Böttcher, Lisa; Rosero, Nathalia; Maasewerd, Salie; Santos, Marina Lima Silva; Próchnicki, Tomasz; Silva, Camila Meirelles de Souza; Wanderley, Carlos Wagner de Souza; Rothe, Maximilian; Schmidt, Susanne V.; Stunden, H. James; Bertheloot, Damien; Rivas, Magali Noval; Fontes, Cor Jésus Fernandes; Carvalho, Luzia H.; Cunha, Fernando Q.; Latz, Eicke; Arditi, Moshe; Franklin, Bernardo S.

doi:10.1016/j.celrep.2020.107615

Cited by 95 publications

(80 citation statements)

References 114 publications

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“…There are emerging studies suggesting the role of platelets as immunomodulators, and platelets can regulate the functions of immune cells such as T cells and macrophages ( Dewi et al, 2020 ; Rolfes et al, 2020 ; Solomou et al, 2020 ). Many studies have proved that platelets have pathogenic roles in some autoimmune diseases such as RA and SLE ( Boilard et al, 2010 ; Duffau et al, 2010 ; Boilard et al, 2012 ; Liu et al, 2020 ), but the potential role of platelets in the pathogenesis of AS has not received much attention.…”

Section: Discussionmentioning

confidence: 99%

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

et al. 2020

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Background: Increased platelet count has been reported in ankylosing spondylitis (AS) patients, but its clinical significance is still largely elusive. The objective of this study was to evaluate the clinical role of platelet count in AS patients, especially its impact on treatment outcomes. Methods: A case-control study containing 35 AS patients receiving anti-tumor necrosis factor-α (anti-TNF-α) therapy and 45 healthy controls was performed, and AS patients were followed at least 6 months after anti-TNF-α therapy. A systematic review and metaanalysis of studies containing relevant data on outcomes of interest was also performed. Results: AS patients had significantly higher platelet count than controls (p 0.0001), and the significantly increased platelet count in AS patients was confirmed in a metaanalysis of 14 studies involving 1,223 AS patients and 913 controls (mean difference 39.61, 95% CI 27.89-51.34, p < 0.001). Besides, platelet count was significantly correlated with ESR (p < 0.001) and was moderately correlated with ASDAS-CRP score (p 0.002). Moreover, anti-TNF-α therapy could reduce platelet count in AS patients at the first month and the effect was maintained through the treatment duration. In the prospective follow-up study of those 35 AS patients, those responders to anti-TNF-α therapy had significantly lower platelet count than nonresponders (p 0.015). Logistic regression analysis suggested that lower platelet count was associated with higher possibility of achieving good response to anti-TNF-α therapy in AS patients (odds ratio 2.26; 95% CI 1.06-4.82; p 0.035). Conclusion: This study suggested that platelet count was associated with inflammation severity and treatment outcomes in AS patients, and elevated platelet count was a promising biomarker of poorer response to anti-TNF-α therapy. The findings above need to be validated in more future studies.

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Section: Discussionmentioning

confidence: 99%

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

et al. 2020

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“…Additionally, platelets are able to license NLRP3 inflammasome activation and IL-1 production in innate immune cells, particularly monocytes. This licensing is via an unknown soluble platelet factor, independent of contact, and is not IL-1 or an inflammasome component (90). Platelets also express IL-1R1, and treatment with exogenous IL-1b can activate platelets and enhance adhesion to substrates (91).…”

Section: Plateletsmentioning

confidence: 99%

Alternative Pathways of IL-1 Activation, and Its Role in Health and Disease

2020

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Cytokines activate or inhibit immune cell behavior and are thus integral to all immune responses. IL-1α and IL-1β are powerful apical cytokines that instigate multiple downstream processes to affect both innate and adaptive immunity. Multiple studies show that IL-1β is typically activated in macrophages after inflammasome sensing of infection or danger, leading to caspase-1 processing of IL-1β and its release. However, many alternative mechanisms activate IL-1α and IL-1β in atypical cell types, and IL-1 function is also important for homeostatic processes that maintain a physiological state. This review focuses on the less studied, yet arguably more interesting biology of IL-1. We detail the production by, and effects of IL-1 on specific innate and adaptive immune cells, report how IL-1 is required for barrier function at multiple sites, and discuss how perturbation of IL-1 pathways can drive disease. Thus, although IL-1 is primarily studied for driving inflammation after release from macrophages, it is clear that it has a multifaceted role that extends far beyond this, with various unconventional effects of IL-1 vital for health. However, much is still unknown, and a detailed understanding of cell-type and context-dependent actions of IL-1 is required to truly understand this enigmatic cytokine, and safely deploy therapeutics for the betterment of human health.

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“…In addition to their role in driving inflammatory thrombosis platelets are key regulators of the innate immune response in both sterile and infectious conditions [20]. The platelet-macrophage interaction has been well described [21] and remains especially relevant to the pathogenesis of the CRS observed in COVID-19 and this is perhaps unsurprising with recent evidence highlighting a clear role for platelets triggering inflammasome activation [22] and then proinflammatory cytokine production that characterizes the CRS [23].…”

mentioning

confidence: 99%