scholarly journals IgA Complexes Induce Neutrophil Extracellular Trap Formation More Potently Than IgG Complexes

2022 ◽  
Vol 12 ◽  
Author(s):  
Anna-Katharina Gimpel ◽  
Antonio Maccataio ◽  
Harald Unterweger ◽  
Maria V. Sokolova ◽  
Georg Schett ◽  
...  

Neutrophil extracellular trap (NET) formation is a powerful instrument to fight pathogens, but may induce collateral damage in the affected tissues. Besides pathogen-derived factors, immune complexes are potent inducers of NET formation. Neutrophils express IgA and IgG specific Fc receptors (FcRs) and therefore respond to complexed IgA and IgG. Especially in the context of autoimmune diseases, IgA and IgG immune complexes have been shown to trigger NET formation, a process that putatively contributes to disease severity. However, it is of question if both antibody classes stimulate neutrophils to the same extent. In this study, we compared the capability of IgA and IgG complexes formed by heat aggregation to induce NET formation. While stimulation of neutrophils with IgA complexes robustly induced NET formation, complexed IgG only marginally increased the amount of NETs compared to the unstimulated control. Mixing IgA with IgG before heat aggregation did not increase the effect of complexed IgA on neutrophils. By contrast, the presence of IgG complexes seemed to disturb neutrophil stimulation by IgA complexes. The capacity of complexed IgG to induce NET formation could not be increased by the addition of autologous serum or the removal of terminal sialic acid in the Fc glycan. Together, our data show that IgA is a much more potent inducer of NET formation than IgG. IgA may thus be the main driving force in (auto)immune complex-mediated NET formation.

2019 ◽  
Vol 220 (12) ◽  
pp. 1999-2008 ◽  
Author(s):  
Carla Cacciotto ◽  
Daniele Dessì ◽  
Tiziana Cubeddu ◽  
Anna Rita Cocco ◽  
Andrea Pisano ◽  
...  

Abstract Mycoplasma lipoproteins play a relevant role in pathogenicity and directly interact with the host immune system. Among human mycoplasmas, Mycoplasma hominis is described as a commensal bacterium that can be associated with a number of genital and extragenital conditions. Mechanisms of M. hominis pathogenicity are still largely obscure, and only a limited number of proteins have been associated with virulence. The current study focused on investigating the role of MHO_0730 as a virulence factor and demonstrated that MHO_0730 is a surface lipoprotein, potentially expressed in vivo during natural infection, acting both as a nuclease with its amino acidic portion and as a potent inducer of Neutrophil extracellular trapsosis with its N-terminal lipid moiety. Evidence for M. hominis neutrophil extracellular trap escape is also presented. Results highlight the relevance of MHO_0730 in promoting infection and modulation and evasion of innate immunity and provide additional knowledge on M. hominis virulence and survival in the host.


2014 ◽  
Vol 193 (4) ◽  
pp. 1954-1965 ◽  
Author(s):  
Martina Behnen ◽  
Christoph Leschczyk ◽  
Sonja Möller ◽  
Tobit Batel ◽  
Matthias Klinger ◽  
...  

Blood ◽  
2014 ◽  
Vol 123 (16) ◽  
pp. 2573-2584 ◽  
Author(s):  
Jan Rossaint ◽  
Jan M. Herter ◽  
Hugo Van Aken ◽  
Markus Napirei ◽  
Yvonne Döring ◽  
...  

Key PointsNET formation is required for neutrophil recruitment during sterile inflammation. Platelet-induced NET formation requires stimulation of neutrophils by platelet chemokines and outside-in signaling via the integrin Mac-1.


Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 505 ◽  
Author(s):  
Besnik Muqaku ◽  
Dietmar Pils ◽  
Johanna C. Mader ◽  
Stefanie Aust ◽  
Andreas Mangold ◽  
...  

It is still a question of debate whether neutrophils, often found in the tumor microenvironment, mediate tumor-promoting or rather tumor-inhibiting activities. The present study focuses on the involvement of neutrophils in high grade serous ovarian cancer (HGSOC). Macroscopic features classify two types of peritoneal tumor spread in HGSOC. Widespread and millet sized lesions characterize the miliary type, while non-miliary metastases are larger and associated with better prognosis. Multi-omics and FACS data were generated from ascites samples. Integrated data analysis demonstrates a significant increase of neutrophil extracellular trap (NET)-associated molecules in non-miliary ascites samples. A co-association network analysis performed with the ascites data further revealed a striking correlation between NETosis-associated metabolites and several eicosanoids. The congruence of data generated from primary neutrophils with ascites analyses indicates the predominance of NADPH oxidase 2 (NOX)-independent NETosis. NETosis is associated with protein S100A8/A9 release. An increase of the S100A8/CRP abundance ratio was found to correlate with favorable survival of HGSOC patients. The analysis of additional five independent proteome studies with regard to S100A8/CRP ratios confirmed this observation. In conclusion, NET formation seems to relate with better cancer patient outcome.


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