Inhibition of meningitis-associated neutrophil apoptosis by TNF-α depends on functional PI3-kinase in monocytes

Recher, Mike; Malipiero, Ursula; Schaer, Dominik J.; Koedel, Uwe; Pfister, Hans‐Walter; Birchler, Thomas; Petrausch, Ulf; Claus, Heike; Gast, Heidemarie; Fontana, Adriano

doi:10.1189/jlb.0511218

Cited by 4 publications

(4 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptotic neurons in the dentate gyrus of the hippocampal formation [ 7 , 8 , 20 , 27 ] and granulocytes in meningeal infiltrates [ 29 , 30 ] were identified by in-situ tailing (IST) and morphology (condensed, shrunken nuclei, condensed and shrunken eosinophilic cytoplasm) [ 31 ]. The sections were counterstained with nuclear fast red-aluminiumhydroxide (Roche, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

The inflammatory response and neuronal injury in Streptococcus suis meningitis

et al. 2018

View full text Add to dashboard Cite

BackgroundMany of the currently used models of bacterial meningitis have limitations due to direct inoculation of pathogens into the cerebrospinal fluid or brain and a relatively insensitive assessment of long-term sequelae. The present study evaluates the utility of a Streptococcus (S.) suis intranasal infection model for the investigation of experimental therapies in meningitis.MethodsWe examined the brains of 10 piglets with S. suis meningitis as well as 14 control piglets by histology, immunohistochemistry and in-situ tailing for morphological alterations in the hippocampal dentate gyrus and microglial activation in the neocortex.ResultsIn piglets with meningitis, the density of apoptotic neurons was significantly higher than in control piglets. Moreover, scoring of microglial morphology revealed a significant activation of these cells during meningitis. The slight increase in the density of dividing cells, young neurons and microglia observed in piglets suffering from meningitis was not statistically significant, probably because of the short time frame between onset of clinical signs and organ sampling.ConclusionsThe morphological changes found during S. suis meningitis are in accordance with abnormalities in other animal models and human autopsy cases. Therefore, the pig should be considered as a model for evaluating effects of experimental therapeutic approaches on neurological function in bacterial meningitis.

show abstract

Section: Methodsmentioning

confidence: 99%

The inflammatory response and neuronal injury in Streptococcus suis meningitis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…108,109 Several other important bacterial pathogens, including Neisseria gonorrhoeae, Neisseria meningitidis, Klebsiella pneumoniae, Treponema pallidum, and Mycobacterium tuberculosis, have also been reported delay neutrophil apoptosis. [110][111][112][113][114][115][116] Some of the bacterial pathogens that prolong neutrophil sur- TNF or GM-CSF. 127 Gamberale et al 128 then showed that precipitating immune complexes and antibody coated erythrocytes also triggered apoptosis in an ROS-dependent manner, albeit phagocytosis was not required.…”

Section: Bacterial Molecules That Promote Survival or Extend The Pmn ...mentioning

confidence: 99%

“…Likewise, the facultative intracellular pathogen F. tularensis delays neutrophil apoptosis in a process specifically dependent on the activity of NF‐κB, PI3Kα, and p38 MAPK 108,109 . Several other important bacterial pathogens, including Neisseria gonorrhoeae , Neisseria meningitidis , Klebsiella pneumoniae , Treponema pallidum , and Mycobacterium tuberculosis , have also been reported delay neutrophil apoptosis 110‐116 …”

Section: Modulation Of Apoptosis By Microorganismsmentioning

confidence: 99%

Microbes and the fate of neutrophils

Kobayashi

DeLeo

Quinn

2022

Immunological Reviews

View full text Add to dashboard Cite

Summary Neutrophils or polymorphonuclear neutrophils (PMNs) are an important component of innate host defense. These phagocytic leukocytes are recruited to infected tissues and kill invading microbes. There are several general characteristics of neutrophils that make them highly effective as antimicrobial cells. First, there is tremendous daily production and turnover of granulocytes in healthy adults—typically 1011 per day. The vast majority (~95%) of these cells are neutrophils. In addition, neutrophils are mobilized rapidly in response to chemotactic factors and are among the first leukocytes recruited to infected tissues. Most notably, neutrophils contain and/or produce an abundance of antimicrobial molecules. Many of these antimicrobial molecules are toxic to host cells and can destroy host tissues. Thus, neutrophil activation and turnover are highly regulated processes. To that end, aged neutrophils undergo apoptosis constitutively, a process that contains antimicrobial function and proinflammatory capacity. Importantly, apoptosis facilitates nonphlogistic turnover of neutrophils and removal by macrophages. This homeostatic process is altered by interaction with microbes and their products, as well as host proinflammatory molecules. Microbial pathogens can delay neutrophil apoptosis, accelerate apoptosis following phagocytosis, or cause neutrophil cytolysis. Here, we review these processes and provide perspective on recent studies that have potential to impact this paradigm.

show abstract

“…However, as these neutrophil functions lack specificity and can be injurious to host tissues, it is important that neutrophil activity be tightly regulated to prevent the perpetuation of inflammation. Actually, neutrophil apoptosis can be delayed at infection sites by a range of factors, including bacterial products such as lipopolysaccharide (LPS) ( 4 ), and pro-inflammatory cytokines ( 5 ), as well as hypoxia ( 6 ), ostensibly to extend their functional lifespan ( 7 ). Once an episode of acute neutrophilic inflammation is complete, it is essential that neutrophil recruitment is halted and that recruited neutrophils undergo apoptosis, before disposal of the apoptotic cells by surrounding phagocytes, such as alveolar macrophages ( 3 , 8 ), to ensure the efficient resolution of inflammation ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of ghrelin on the apoptosis of human neutrophils in vitro

Zeng

Zheng

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and the diffuse infiltration of neutrophils into the alveolar space. Neutrophils are abundant, short-lived leukocytes that play a key role in immune defense against microbial infections. These cells die via apoptosis following the activation and uptake of microbes, and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter pathogens. Apoptosis is essential for the removal of neutrophils from inflamed tissues and for the timely resolution of neutrophilic inflammation. Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor, produced and secreted mainly from the stomach. Previous studies have reported that ghrelin exerts anti-inflammatory effects in lung injury through the regulation of the apoptosis of different cell types; however, the ability of ghrelin to regulate alveolar neutrophil apoptosis remains largely undefined. We hypothesized that ghrelin may have the ability to modulate neutrophil apoptosis. In this study, to examine this hypothesis, we investigated the effects of ghrelin on freshly isolated neutrophils in vitro. Our findings demonstrated a decrease in the apoptotic ratio (as shown by flow cytometry), as well as in the percentage of cells with decreased mitochondrial membrane potential (ΔΨm) and in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling-positive rate, accompanied by an increased B-cell lymphoma 2/Bax ratio and the downregulation of cleaved caspase-3 in neutrophils following exposure to lipopolysaccharide (100 ng/ml). However, pre-treatment with ghrelin at a physiological level (100 nM) did not have a notable influence on the neutrophils in all the aforementioned tests. Our findings suggest that ghrelin may not possess the ability to modulate the neutrophil lifespan in vitro.

show abstract

Inhibition of meningitis-associated neutrophil apoptosis by TNF-α depends on functional PI3-kinase in monocytes

Cited by 4 publications

References 31 publications

The inflammatory response and neuronal injury in Streptococcus suis meningitis

The inflammatory response and neuronal injury in Streptococcus suis meningitis

Microbes and the fate of neutrophils

Effects of ghrelin on the apoptosis of human neutrophils in vitro

Contact Info

Product

Resources

About