A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3

Verschoor, Admar; Neuenhahn, Michael; Navarini, Alexander A.; Graef, Patricia; Plaumann, Ann; Seidlmeier, Amelie; Nieswandt, Bernhard; Maßberg, Steffen; Zinkernagel, Rolf M.; Hengartner, Hans; Busch, Dirk H.

doi:10.1038/ni.2140

Cited by 177 publications

(176 citation statements)

References 48 publications

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“…Because complement is involved in phagocytosis and killing of C3-bound L. monocytogenes by activated macrophages (42) and is required for the efficient generation of CD8 + T cell responses (35), it is reasonable to hypothesize that C3 2/2 mice acquire greater bacterial loads after L. monocytogenes infections. Surprisingly, the bacterial load was significantly lower in the spleen of C3 2/2 mice than in WT mice postinfection because of reduced blood-borne bacterial shuttling to splenic CD8a + DCs (30). We speculated that bacterial loads might not correlate with the protective function of effector CD8 + T cells in the model of L. monocytogenes infection.…”

Section: Memory Cd8 + T Cells Function Normally In C3 2/2 Micementioning

confidence: 73%

“…In contrast, optimal CD8 + T cell responses against visceral leishmaniasis depend on circulating complement activation by natural Abs (29). Moreover, C3 depletion by cobra venom factor (CVF) treatment or C3 deficiency lead to weak CD8 + T cell responses because fewer blood-borne bacteria are transferred to splenic CD8a + dendritic cells (DCs) postinfection (30). Therefore, it is important to determine the roles of systemic and local C3 production in the regulation of the CD8 + T cell response, because they may inform the design of more effective vaccines.…”

Section: /2mentioning

confidence: 99%

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Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Tan

et al. 2014

The Journal of Immunology

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Ag-specific CD8+ T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8+ T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3−/−) mice exhibited significantly less CD8+ T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3−/− recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3−/− mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8+ T cells. However, reduced contraction in C3−/− mice was accompanied by a decrease in the proportion of KLRG-1hi (killer-cell lectin-like receptor G1) CD127lo short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.

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Section: Memory Cd8 + T Cells Function Normally In C3 2/2 Micementioning

confidence: 73%

Section: /2mentioning

confidence: 99%

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Tan

et al. 2014

The Journal of Immunology

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“…They can stimulate adaptive immunity by tagging bacteria and shuttling them to CD8a + dendritic cells in the spleen (Fig. 3) [71]. In response to bacterial infection, platelets, like myeloid cells, recognize DAMPs via pattern recognition receptors, for example, by binding of LPS to TLR4.…”

Section: Platelets Modulate Blood Coagulation and Innate Immunitymentioning

confidence: 99%

Crossroads of coagulation and innate immunity: the case of deep vein thrombosis

Schulz

Engelmann

Maßberg

2013

Journal of Thrombosis and Haemostasis

107

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Summary Deep vein thrombosis (DVT) is a common condition characterized by the formation of an occlusive blood clot in the venous vascular system, potentially complicated by detachment and embolization of thrombi into the lung. Recent evidence from mouse models has shed light on the sequence of events and on the cellular (innate immune cells, platelets) and molecular (hematopoietic tissue factor, nucleic acids) components involved. In response to decreased blood flow, circulating neutrophils and monocytes adhere to the activated endothelium within hours. They initiate and propagate DVT by interacting with platelets and by the exposure and activation of circulating tissue factor and FXII. Intravascular blood coagulation is also induced by extracellular nucleosomes released mainly from activated neutrophils. Interestingly, these mechanisms are closely linked to an evolutionary conserved immune defense mechanism activated in response to infections. In this review, we will give an overview of DVT and the role of innate immune pathways supporting this process. While the latter are aimed at preserving tissue integrity and function, uncontrolled blood coagulation and activation of immune cells may result in pathological thrombus formation and vascular occlusion. Understanding the molecular and cellular players triggering occlusion of large veins, and their distinction from physiological hemostasis, is important for the development of strategies to prevent and treat DVT.

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“…It is becoming increasingly clear that to achieve these infection-limiting effects, interactions extend well beyond the familiar collaboration between platelets, coagulation, and fibrinolysis in hemostasis. For instance, detailed in vivo and in vitro studies documented how collaboration between platelets and complement 4 or von Willebrand factor 5 helps target intravascular bacteria to phagocytes, that complement activates platelets and vice versa, 6 and that plasmin 2 and thrombin 3 can in principle activate complement.…”

Section: Universität Zu Lübeckmentioning

confidence: 99%

Complement and coagulation: so close, yet so far

Schmidt¹,

Verschoor

2017

Blood

Self Cite

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5. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21(7):677-687.6. van Hout GP, Bosch L, Ellenbroek GH, et al. The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. Eur Heart J. 2017;38(11):828-836.7. Wang J, Yang L, Rezaie AR, Li J. Activated protein C protects against myocardial ischemic/reperfusion injury through AMP-activated protein kinase signaling.

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A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3

Cited by 177 publications

References 48 publications

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Crossroads of coagulation and innate immunity: the case of deep vein thrombosis

Complement and coagulation: so close, yet so far

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