scholarly journals Toxoplasma gondii-Induced Neutrophil Extracellular Traps Amplify the Innate and Adaptive Response

mBio ◽  
2021 ◽  
Author(s):  
Farlen J. B. Miranda ◽  
Bruno C. Rocha ◽  
Milton C. A. Pereira ◽  
Larissa M. N. Pereira ◽  
Erikson H. M. de Souza ◽  
...  

Approximately one-third of the human population is estimated to be chronically infected with the obligate intracellular parasite Toxoplasma gondii . Humans are accidental hosts that are infected with T. gondii after consumption of undercooked meat or contaminated water.

2012 ◽  
Vol 80 (11) ◽  
pp. 3921-3929 ◽  
Author(s):  
Donporn Riyapa ◽  
Surachat Buddhisa ◽  
Sunee Korbsrisate ◽  
Jon Cuccui ◽  
Brendan W. Wren ◽  
...  

ABSTRACTBurkholderia pseudomalleiis the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. Polymorphonuclear neutrophils (PMNs) kill microbes extracellularly by the release of neutrophil extracellular traps (NETs). PMNs play a key role in the control of melioidosis, but the involvement of NETs in killing ofB. pseudomalleiremains obscure. Here, we showed that bactericidal NETs were released from human PMNs in response toB. pseudomalleiin a dose- and time-dependent manner.B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways.B. pseudomalleimutants defective in the virulence-associated Bsa type III protein secretion system (T3SS) or capsular polysaccharide I (CPS-I) induced elevated levels of NETs. NET induction by such mutants was associated with increased bacterial killing, phagocytosis, and oxidative burst by PMNs. Taken together the data imply that T3SS and the capsule may play a role in evading the induction of NETs. Importantly, PMNs from diabetic subjects released NETs at a lower level than PMNs from healthy subjects. Modulation of NET formation may therefore be associated with the pathogenesis and control of melioidosis.


2014 ◽  
Vol 13 (8) ◽  
pp. 965-976 ◽  
Author(s):  
Ira J. Blader ◽  
Anita A. Koshy

ABSTRACTIntracellular pathogens can replicate efficiently only after they manipulate and modify their host cells to create an environment conducive to replication. While diverse cellular pathways are targeted by different pathogens, metabolism, membrane and cytoskeletal architecture formation, and cell death are the three primary cellular processes that are modified by infections.Toxoplasma gondiiis an obligate intracellular protozoan that infects ∼30% of the world's population and causes severe and life-threatening disease in developing fetuses, in immune-comprised patients, and in certain otherwise healthy individuals who are primarily found in South America. The high prevalence ofToxoplasmain humans is in large part a result of its ability to modulate these three host cell processes. Here, we highlight recent work defining the mechanisms by whichToxoplasmainteracts with these processes. In addition, we hypothesize why some processes are modified not only in the infected host cell but also in neighboring uninfected cells.


1995 ◽  
Vol 108 (6) ◽  
pp. 2457-2464 ◽  
Author(s):  
J.H. Morisaki ◽  
J.E. Heuser ◽  
L.D. Sibley

Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of vertebrate cells including macrophages. We have used a combination of video microscopy and fluorescence localization to examine the entry of Toxoplasma into macrophages and nonphagocytic host cells. Toxoplasma actively invaded host cells without inducing host cell membrane ruffling, actin microfilament reorganization, or tyrosine phosphorylation of host proteins. Invasion occurred rapidly and within 25–40 seconds the parasite penetrated into a tight-fitting vacuole formed by invagination of the plasma membrane. In contrast, during phagocytosis of Toxoplasma, extensive membrane ruffling captured the parasite in a loose-fitting phagosome that formed over a period of 2–4 minutes. Phagocytosis involved both reorganization of the host cytoskeleton and tyrosine phosphorylation of host proteins. In some cases, parasites that were first internalized by phagocytosis, were able to escape from the phagosome by a process analogous to invasion. These studies reveal that active penetration of the host cell by Toxoplasma is fundamentally different from phagocytosis or induced endocytic uptake. The novel ability to penetrate the host cell likely contributes to the capability of Toxoplasma-containing vacuoles to avoid endocytic processing.


1995 ◽  
Vol 15 (1) ◽  
pp. 87-93 ◽  
Author(s):  
D Soldati ◽  
J C Boothroyd

The recent development of an efficient transfection system for the apicomplexan Toxoplasma gondii allows a comprehensive dissection of the elements involved in gene transcription in this obligate intracellular parasite. We demonstrate here that for the SAG1 gene, a stretch of six repeated sequences in the region 35 to 190 bp upstream of the first of two transcription start sites is essential for efficient and accurate transcription initiation. This repeat element shows characteristics of a selector in determining the position of the transcription start sites.


2015 ◽  
Vol 83 (9) ◽  
pp. 3648-3656 ◽  
Author(s):  
Ding Xu ◽  
Joshua Olson ◽  
Jason N. Cole ◽  
Xander M. van Wijk ◽  
Volker Brinkmann ◽  
...  

Recently, we showed that endothelial heparan sulfate facilitates entry of a bacterial pathogen into the central nervous system. Here, we show that normal bactericidal activity of neutrophils is influenced by the sulfation pattern of heparan sulfate. Inactivation of heparan sulfate uronyl 2-O-sulfotransferase (Hs2st) in neutrophils substantially reduced their bactericidal activity, and Hs2st deficiency rendered mice more susceptible to systemic infection with the pathogenic bacterium group BStreptococcus. Specifically, altered sulfation of heparan sulfate in mutant neutrophils affected formation of neutrophil extracellular traps while not influencing phagocytosis, production of reactive oxygen species, or secretion of granular proteases. Heparan sulfate proteoglycan(s) is present in neutrophil extracellular traps, modulates histone affinity, and modulates their microbial activity. Hs2st-deficient brain endothelial cells show enhanced binding to group BStreptococcusand are more susceptible to apoptosis, likely contributing to the observed increase in dissemination of group BStreptococcusinto the brain of Hs2st-deficient mice following intravenous challenge. Taken together, our data provide strong evidence that heparan sulfate from both neutrophils and the endothelium plays important roles in modulating innate immunity.


2021 ◽  
Vol 854 (1) ◽  
pp. 012008
Author(s):  
N Betic ◽  
I Klun ◽  
V Djordjevic ◽  
I Brankovic Lazic ◽  
T Baltic ◽  
...  

Abstract Infection with the apicomplexan protozoon Toxoplasma gondii is one of the most prevalent parasitic zoonotic infections globally, with existing seroprevalences varying between continents, countries, and even within countries and between individual communities. It is estimated that one third of the world’s human population is infected with T. gondii, with many studies showing that the dominant mode of infection is consumption of undercooked meat harbouring T. gondii tissue cysts. Prevalences of infection in food animals in different countries range from 0 to 93%. Because of the absence of clinical symptoms in infected animals, and the unfeasibility of rapid and unequivocal detection of microscopic tissue cysts in pork, infected pigs remain unrecognized, and their meat becomes an essential source of infection for humans. The data on T. gondii infection in pigs in Serbia from several studies, as well as on the detection of the parasite in different food categories, from fresh pork to heat-treated products, are discussed.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yang Wang ◽  
Jinjin Zhu ◽  
Yuanyuan Cao ◽  
Jilong Shen ◽  
Li Yu

Inflammasomes are multimeric protein complexes regulating the innate immune response to invading pathogens or stress stimuli. Recent studies have reported that nucleotide-binding leucine-rich repeat-containing (NLRs) proteins and DNA sensor absent in melanoma 2 (AIM2) serve as inflammasome sentinels, whose stimulation leads to the proteolytic activation of caspase-1, proinflammatory cytokine secretion, and pyroptotic cell death. Toxoplasma gondii, an obligate intracellular parasite of phylum Apicomplexans, is reportedly involved in NLRP1, NLRP3 and AIM2 inflammasomes activation; however, mechanistic evidence regarding the activation of these complexes is preliminary. This review describes the current understanding of inflammasome signaling in rodent and human models of T. gondii infection.


mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Hee-Jin Park ◽  
Weiwei Wang ◽  
Gilberto Curlango-Rivera ◽  
Zhongguo Xiong ◽  
Zeran Lin ◽  
...  

ABSTRACT Histone-linked extracellular DNA (exDNA) is a component of neutrophil extracellular traps (NETs). NETs have been shown to play a role in immune response to bacteria, fungi, viruses, and protozoan parasites. Mutation of genes encoding group A Streptococcus extracellular DNases (exDNases) results in reduced virulence in animals, a finding that implies that exDNases are deployed as counter defense against host DNA-containing NETs. Is the exDNA/exDNase mechanism also relevant to plants and their pathogens? It has been demonstrated previously that exDNA is a component of a matrix secreted from plant root caps and that plants also carry out an extracellular trapping process. Treatment with DNase I destroys root tip resistance to infection by fungi, the most abundant plant pathogens. We show that the absence of a single gene encoding a candidate exDNase results in significantly reduced virulence of a fungal plant pathogen to its host on leaves, the known infection site, and on roots. Mg2+-dependent exDNase activity was demonstrated in fungal culture filtrates and induced when host leaf material was present. It is speculated that the enzyme functions to degrade plant-secreted DNA, a component of a complex matrix akin to neutrophil extracellular traps of animals. IMPORTANCE We document that the absence of a single gene encoding a DNase in a fungal plant pathogen results in significantly reduced virulence to a plant host. We compared a wild-type strain of the maize pathogen Cochliobolus heterostrophus and an isogenic mutant lacking a candidate secreted DNase-encoding gene and demonstrated that the mutant is reduced in virulence on leaves and on roots. There are no previous reports of deletion of such a gene from either an animal or plant fungal pathogen accompanied by comparative assays of mutants and wild type for alterations in virulence. We observed DNase activity, in fungal culture filtrates, that is Mg2+ dependent and induced when plant host leaf material is present. Our findings demonstrate not only that fungi use extracellular DNases (exDNases) for virulence, but also that the relevant molecules are deployed in above-ground leaves as well as below-ground plant tissues. Overall, these data provide support for a common defense/counter defense virulence mechanism used by animals, plants, and their fungal and bacterial pathogens and suggest that components of the mechanism might be novel targets for the control of plant disease.


Author(s):  
Zuhair Dardona ◽  
Samia BOUSSAA ◽  
Adnan Al-Hindi ◽  
Ali aboumezzough ◽  
Mohamed Hafidi

Toxoplasma gondii  a ubiquitous obligate intracellular parasite that can infect all warm-blooded animals, is one of the main pathogens causing foodborne diseases worldwide. In Gaza – Palestine, the leafy vegetables are frequently eaten raw.  The present study was carried out to investigate the occurrence of T. gondii oocyst in local leafy vegetables. For this purpose, fifty samples of each kind of six different leafy plants sold in markets, supermarkets, and retail sellers were randomly collected during the period from March to August 2019. , the three hundred samples were collected from six different species of leafy vegetables. The samples were examined microscopy through using a light microscope and after performing the flotation technique of Sheather's solution to easily detect the oocysts, the suspected samples were confirmed by using PCR technique. Upon analyzing the samples and using the PCR method, only 19 out of the 300 samples (6.33 %) were found to be contaminated, whereas by using Sheather's solution method, 35 out of the 300 samples (11.66%) were contaminated. Among the six various plants and according to the PCR method, mint held the highest rate of contamination (10.00 %), followed by both watercress and dill with a similar percentage (8.00%), parsley (6.00%), thyme (4.00%),  and finally, lettuce carrying the lowest rate (2.00%). Even though the sequence among those contaminated plants was found similar in the PCR and the Sheather's solution, the rates were different. With this method, mint stood at (18.00%), watercress (14.00%), dill (13.00%), parsley (10.00%), thyme (10.00%) and lettuce (6.00%). Moreover, the present study has reported that the relationship between the period of collection and T. gondii contamination is statistically significant. Whereby, the highest rate of contamination recorded was in July, followed by June, then August. Based on the findings of the present study, leafy vegetables are quite vulnerable to T. gondii contamination.


Sign in / Sign up

Export Citation Format

Share Document