Immune complex‐induced neutrophil functions: A focus on cell death

Vermeren, Sonja; Karmakar, Utsa; Rossi, Adriano G.

doi:10.1111/eci.12948

Cited by 12 publications

(16 citation statements)

References 74 publications

(135 reference statements)

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“…However, the mechanistic process that governs such switching is not understood. Immune complexes consisting of antibody–antigen pairs are powerful stimulators of immune cells, which can release a burst of ROS ( 52 , 53 ). Interestingly, we observed an increase in Pf TPx-1 expression following exposure to different sources of oxidative stress ( SI Appendix , Fig.…”

Section: Discussionmentioning

confidence: 99%

A nuclear redox sensor modulates gene activation andvarswitching inPlasmodium falciparum

Heinberg¹,

Amit-Avraham²,

Mitesser³

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The virulence of Plasmodium falciparum , which causes the deadliest form of human malaria, is attributed to its ability to evade the human immune response. These parasites “choose” to express a single variant from a repertoire of surface antigens called PfEMP1, which are placed on the surface of the infected red cell. Immune evasion is achieved by switches in expression between var genes, each encoding a different Pf EMP1 variant. While the mechanisms that regulate mutually exclusive expression of var genes are still elusive, antisense long-noncoding RNAs (lncRNAs) transcribed from the intron of the active var gene were implicated in the “choice” of the single active var gene. Here, we show that this lncRNA colocalizes with the site of var mRNA transcription and is anchored to the var locus via DNA:RNA interactions. We define the var lncRNA interactome and identify a redox sensor, P. falciparum thioredoxin peroxidase I ( Pf TPx-1), as one of the proteins associated with the var antisense lncRNA. We show that Pf TPx-1 localizes to a nuclear subcompartment associated with active transcription on the nuclear periphery, in ring-stage parasite, when var transcription occurs. In addition, Pf TPx-1 colocalizes with S-adenosylmethionine synthetase ( Pf SAMS) in the nucleus, and its overexpression leads to activation of var2csa, similar to overexpression of Pf SAMS. Furthermore, we show that Pf TPx-1 knockdown alters the var switch rate as well as activation of additional gene subsets. Taken together, our data indicate that nuclear Pf TPx-1 plays a role in gene activation possibly by providing a redox-controlled nuclear microenvironment ideal for active transcription.

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Section: Discussionmentioning

confidence: 99%

A nuclear redox sensor modulates gene activation andvarswitching inPlasmodium falciparum

Heinberg¹,

Amit-Avraham²,

Mitesser³

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Spontaneous apoptosis which could be quite different from phagocytosis‐induced apoptosis by microbes or immune complexes. Whereas spontaneous apoptosis does not trigger an inflammatory response, phagocytosis‐induced apoptosis generates proinflammatory events, such as neutrophil degranulation, ROS production and inflammatory mediator production . Trafficking of senescent neutrophils cleared from the circulation may persist in specific tissues under homeostasis and disease and modulate immunity .…”

Section: Discussionmentioning

confidence: 99%

“…Whereas spontaneous apoptosis does not trigger an inflammatory response, phagocytosis-induced apoptosis generates proinflammatory events, such as neutrophil degranulation, ROS production and inflammatory mediator production. 94 Trafficking of senescent neutrophils cleared from the circulation may persist in specific tissues under homeostasis and disease and modulate immunity. 95,96 In this review, we have highlighted some of these molecules and their beneficial or detrimental actions.…”

Section: Discussionmentioning

confidence: 99%

Regulation of macrophage activation by proteins expressed on apoptotic neutrophils: Subversion towards autoimmunity by proteinase 3

Thiéblemont

Witko‐Sarsat

Ariel

2018

Eur J Clin Investigation

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Neutrophils are critically involved in host defence and they also modulate the inflammatory process. Turning the inflammatory response towards a resolutive outcome requires a dialogue between apoptotic neutrophils and proresolving macrophages through complex key molecular interactions controlling efferocytosis, anti-inflammatory reprogramming and ultimately immune regulation. In this review, we will first focus on recent molecular analyses aiming at characterizing the role of proteins expressed on apoptotic neutrophils and their cognate partners expressed on macrophages in the resolution of inflammation. These will include chemokine receptors and their ligands and annexin A1 and its receptor FPR2. We will next depict how the structural and enzymatic properties of proteinase 3 (PR3), the autoantigen in vasculitis, allow its expression on apoptotic neutrophils, which in turn affects efferocytosis and immune response associated with the clearance of apoptotic cells. This example illustrates that the fate of apoptotic neutrophils directly influences the resolution of inflammation and immune responses thereby potentially contributing to systemic and nonresolving inflammation as well as autoimmunity.

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“…Haemolysis occurs intracellularly or through antibody-dependent cell-mediated cytotoxicity, a process whereby the phagocyte secretes reactive oxygen species (ROS) and other cytotoxic molecules that can cause haemolysis and might be harmful for the surrounding microenvironment amplifying the pro-inflammatory response [54]. Next to ROS production, triggering of FcRs by immune complexes may result in the generation of pro-inflammatory Neutrophil extracellular traps (NETs) [54]. Occasionally, downstream complement activation beyond C3 may result in terminal complement activation with subsequent intravascular haemolysis (Fig.…”

Section: Complement and Immune Haemolytic Anaemiamentioning

confidence: 99%

The interplay between the innate immune system and immune haemolytic anaemia

Delvasto-Núñez

Jongerius

2020

ISBT Science Series

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Immune haemolytic anaemia (IHA) is characterized by an increased breakdown of red blood cells (RBCs) due to allo-or auto-antibodies directed to RBC antigens with or without complement activation. Based on the nature of the antibodies, IHA can be divided in three main categories: autoimmune, drug-induced and alloimmune-mediated IHA. There is growing evidence that the innate immune system plays an important role in the pathogenesis of IHA. Complement-mediated haemolysis with the subsequent release of cell-free haemoglobin and cellfree haem resulting in the generation of reactive oxygen species and cytotoxicity as well as the production of anaphylatoxins induce a systemic inflammatory response, which contributes to morbidity and mortality in IHA. The natural plasma scavengers of cell-free haemoglobin and cell-free haem, haptoglobin and hemopexin, respectively, are depleted in cases of chronic or severe IHA. The inducible enzyme haem oxygenase 1 (HO-1) is an efficient cellular scavenger degrading haem into anti-inflammatory products to partially limit haemmediated oxidative damage in cases of saturated scavenging capacity. Complement-targeted therapy and the therapeutic replenishment of haptoglobin and hemopexin as well as the induction of HO-1 expression might be suitable targets in the treatment of IHA.

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Immune complex‐induced neutrophil functions: A focus on cell death

Cited by 12 publications

References 74 publications

A nuclear redox sensor modulates gene activation andvarswitching inPlasmodium falciparum

A nuclear redox sensor modulates gene activation andvarswitching inPlasmodium falciparum

Regulation of macrophage activation by proteins expressed on apoptotic neutrophils: Subversion towards autoimmunity by proteinase 3

The interplay between the innate immune system and immune haemolytic anaemia

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