Neutrophil extracellular trap formation as innate immune reactions against the apicomplexan parasite Eimeria bovis

Behrendt, Jan Hillern; Ruiz, Antonio; Zahner, Horst; Taubert, Anja; Hermosilla, Carlos

doi:10.1016/j.vetimm.2009.06.012

Cited by 120 publications

(117 citation statements)

References 35 publications

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“…To date, bacteria, fungi, viruses, and protozoan parasites have been shown to induce NETosis in neutrophils (2,4,12,13,(40)(41)(42)(43). Among parasites, Leishmania spp., Eimeria bovis, and Toxoplasma gondii were reported to activate NETosis (12, 13, 40, 41).…”

Section: Discussionmentioning

confidence: 99%

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

et al. 2014

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Leishmaniasis is a widespread neglected tropical disease caused by parasites of the Leishmania genus. These parasites express the enzyme 3=-nucleotidase/nuclease (3=NT/NU), which has been described to be involved in parasite nutrition and infection. Bacteria that express nucleases escape the toxic effects of neutrophil extracellular traps (NETs). Hence, we investigated the role of 3=NT/NU in Leishmania survival of NET-mediated killing. Promastigotes of Leishmania infantum were cultured in high-phosphate (HP) or low-phosphate (LP) medium to modulate nuclease activity. We compared the survival of the two different groups of Leishmania during interaction with human neutrophils, assessing the role of neutrophil extracellular traps. As previously reported, we detected higher nuclease activity in parasites cultured in LP medium. Both LP and HP promastigotes were capable of inducing the release of neutrophil extracellular traps from human neutrophils in a dose-and time-dependent manner. LP parasites had 2.4 times more survival than HP promastigotes. NET disruption was prevented by the treatment of the parasites with ammonium tetrathiomolybdate (TTM), a 3=NT/NU inhibitor. Inhibition of 3=NT/NU by 3=-AMP, 5=-GMP, or TTM decreased promastigote survival upon interaction with neutrophils. Our results show that Leishmania infantum induces NET release and that promastigotes can escape NET-mediated killing by 3=-nucleotidase/nuclease activity, thus ascribing a new function to this enzyme. N eutrophils are short-lived cells and the most abundant leukocytes in the blood circulation; they constitute one of the first lines of defense against invading microorganisms (1). These granulocytes can kill microorganisms by phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are weblike structures composed of chromatin, granules, and cytoplasmic proteins that are extruded when neutrophils undergo NETosis, a unique cell death mechanism (2-5). However, recent work challenges NETosis as a cell death mechanism because live neutrophils were detected after NET extrusion in in vivo studies (6). NETs function by killing and containing pathogens, thereby preventing the pathogen's dissemination through the organism. In addition, some studies have indicated that NETs play a role in autoimmune diseases (7-10).A diverse group of stimuli has been described as activating NETosis (5, 11). Among the parasites, Leishmania promastigotes were demonstrated to activate release of NETs (12, 13). Leishmania amazonensis promastigotes interact intimately with NETs and are killed by web-associated histones (12). However, although promastigotes of Leishmania donovani trigger NET release, these parasites escape the toxicity of NETs (13). Groups of microorganisms have evolved different mechanisms of escaping the toxic effects of NETs. Streptococcus pneumoniae, group A Streptococcus, Streptococcus agalactiae, Staphylococcus aureus, and Vibrio cholerae express endonucleases that efficiently degrade DNA filaments from NETs, allowing these bacteria...

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Section: Discussionmentioning

confidence: 99%

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

et al. 2014

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“…PMNs were separated from blood as described by Behrendt et al [12]. Holstein cows were bled by puncture of the jugular vein and blood was collected in a 50-mL centrifuge tube (Nunc, Roskilde, Denmark) containing 0.1 mL heparin (Sigma-Aldrich, St. Louis, MO) as an anticoagulant.…”

Section: Isolation and Culture Of Pmnsmentioning

confidence: 99%

Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dairy cows with clinical ketosis display a negative energy balance and high blood concentrations of non-esterified fatty acids (NEFAs), the latter of which is an important pathological factor of ketosis in cows. The aims of this study were to investigate the inflammatory status of ketotic cows and to determine whether and through what underlying mechanism high levels of NEFAs induce an inflammatory response. Methods: Proinflammatory factors and the nuclear factor kappa B (NF-κB) signaling pathway were evaluated in neutrophils from clinical ketotic and control cows, using methods including western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. In vitro, the effects of NEFAs on the NF-κB signaling pathway in cow neutrophils were also evaluated using the above experimental techniques. Results: Ketotic cows displayed low blood concentrations of glucose and high blood NEFA and β-hydroxybutyrate concentrations. Importantly, Toll-like receptor 2 (TLR2) and TLR4 expression and IκBα and NF-κB p65 phosphorylation levels in neutrophils (PMNs) were significantly higher in ketotic cows than in control cows, indicating over-activation of the TLR2/4-induced NF-κB inflammatory pathway in PMNs in ketotic cows. The blood concentrations of the inflammatory cytokines interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were also significantly increased in ketotic cows. Interestingly, we found that NEFAs were positively correlated with proinflammatory cytokines. In vitro, after pharmacological inhibition of TLR2 and TLR4 expression in cow neutrophils, TLR2 and TLR4 expression was significantly decreased, and the phosphorylation level of NF-κB p65 was also reduced. Cow neutrophils were treated with different concentrations of NEFAs and pyrrolidine dithiocarbamate (PDTC; an NF-κB inhibitor). High concentrations of NEFAs (0.5 and 1 mM) significantly increased TLR2 and TLR4 expression, IκBα and NF-κB p65 phosphorylation levels, NF-κB p65 transcriptional activity, and IL-6, IL-1β, and TNF-α synthesis in cow neutrophils. The inhibition of NF-κB by PDTC suppressed the NEFA-induced synthesis of proinflammatory cytokines. Conclusions: High concentrations of NEFAs can over-activate the TLR2/4-mediated NF-κB signaling pathway to induce the over-production of proinflammatory cytokines, thereby increasing inflammation in cows with clinical ketosis.

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“…The phagocytosis of Eimeria by macrophages has also been clearly demonstrated in cattle, independent of the presence of immune serum (Behrendt et al 2008) and augmented by immune serum (Taubert et al 2009). More recently, the roles of neutrophils in resistance to bovine Eimeria were shown to include neutrophil extracellular trap (NET) activity on sporozites of E. bovis with subsequent decreased parasite infectivity in vitro (Behrendt et al 2010). However, the roles of neutrophils and macrophages have not been demonstrated in infection and challenge studies with naive animals.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Toltrazuril 5 % Suspension against Eimeria bovis and Eimeria zuernii in Calves and Observations on the Associated Immunopathology

et al. 2011

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16 Calves were each infected with suspensions containing a mixture of approximately 230,000 Eimeria bovis and 70,000 E. zuernii oocysts, which resulted in detection of oocysts in faeces of 12 of 16 calves by day +14 after infection. On day +14 after infection calves were either treated (n = 8) with toltrazuril at 15 mg/kg body weight or with a placebo. Observations were made on the clinical condition, faecal score and liveweight of calves daily from one day post infection (pi) until 24 days pi when all calves were euthanised and examined post mortem. Samples were collected from ileum and colon for histological, immunohistochemical and gene expression studies. The study demonstrated an efficacy of toltrazuril for the treatment of E. bovis and E. zuernii infections in calves reaching 99 % (based on arithmetic mean oocyst counts in faeces) within three days of treatment and remaining at or above this level for six days. Toltrazuril did not have a significant effect on the pattern and extent of immune cellular infiltration in the mucosa of ileum and colon, but the expression of the genes coding IL-2, IL-10 and TNF-α in the ileum and TNF-α in the colon were elevated in calves treated with toltrazuril. Higher levels of oocyst shedding were significantly associated with lower expression of genes coding for IL-2, IL-10 and higher IP-10. It is concluded that toltrazuril is effective for the treatment of coccidiosis due to E. bovis and E. zuernii in calves and enables the development of a normal or enhanced immune response to infection.

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Neutrophil extracellular trap formation as innate immune reactions against the apicomplexan parasite Eimeria bovis

Cited by 120 publications

References 35 publications

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

Efficacy of Toltrazuril 5 % Suspension against Eimeria bovis and Eimeria zuernii in Calves and Observations on the Associated Immunopathology

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