Review on the immunological and molecular diagnosis of neosporosis (years 2011–2016)

Sinnott, Francine Alves; Monte, Leonardo Garcia; Collares, Thaís Farias; Silveira, Roberta Maraninchi; Borsuk, Sibele

doi:10.1016/j.vetpar.2017.04.008

Cited by 33 publications

(24 citation statements)

References 85 publications

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“…Although NcSAG1 was not present on the MNC surface anymore, the triple-layered plasma membrane was still present and intact after nine days of drug treatment as shown by TEM (see also [10]). Thus, it is conceivable that (an)other member(s) of the surface antigen glycoprotein-related sequences (SRS) superfamily could potentially be expressed on the surface of these complexes ( [20]).…”

Section: Discussionmentioning

confidence: 99%

Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294

et al. 2020

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Background: Bumped kinase inhibitors (BKIs) are potential drugs for neosporosis treatment in farm animals. BKI-1294 exposure results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs, the re-emergence of viable tachyzoites following drug removal, and the localization of CDPK1, the molecular target of BKIs. Methods: N. caninum tachyzoites and MNCs were studied by TEM and immunofluorescence using antibodies directed against CDPK1, and against NcSAG1 and IMC1 as markers for tachyzoites and newly formed zoites, respectively. Results: After six days of drug exposure, MNCs lacked SAG1 surface expression but remained intracellular, and formed numerous zoites incapable of disjoining from each other. Following drug removal, proliferation continued, and zoites lacking NcSAG1 emerged from the periphery of these complexes, forming infective tachyzoites after 10 days. In intracellular tachyzoites, CDPK1 was evenly distributed but shifted towards the apical part once parasites were extracellular. This shift was not affected by BKI-1294. Conclusions: CDPK1 has a dynamic distribution depending on whether parasites are located within a host cell or outside. During MNC-to-tachyzoite reconversion newly formed tachyzoites are generated directly from MNCs through zoites of unknown surface antigen composition. Further in vivo studies are needed to determine if MNCs could lead to a persistent reservoir of infection after BKI treatment.

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Section: Discussionmentioning

confidence: 99%

Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294

et al. 2020

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“…Neospora caninum is an apicomplexan parasite that infects a broad range of warm-blooded animals and leads to neosporosis worldwide ( 1 – 3 ). N. caninum usually progresses through three stages: tachyzoite, bradyzoite, and sporozoite.…”

Section: Introductionmentioning

confidence: 99%

NLRP3 Inflammasome Participates in Host Response to Neospora caninum Infection

et al. 2018

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Neospora caninum is an intracellular protozoan parasite closely related to Toxoplasma gondii that mainly infects canids as the definitive host and cattle as the intermediate host, resulting in abortion in cattle and leading to financial losses worldwide. Commercial vaccines or drugs are not available for the prevention and treatment of bovine neosporosis. Knowledge about the hallmarks of the immune response to this infection could form the basis of important prevention strategies. The innate immune system first responds to invading parasite and subsequently initiates the appropriate adaptive immune response against this parasite. Upon infection, activation of host pattern-recognition receptors expressed by immune cells triggers the innate immune response. Toll-like receptors, NOD-like receptors, and C-type lectin receptors play key roles in recognizing protozoan parasite. Therefore, we aimed to explore the role of the NLRP3 inflammasome during the acute period of N. caninum infection. In vitro results showed that N. caninum infection of murine bone marrow-derived macrophages activated the NLRP3 inflammasome, accompanied by the release of IL-1β and IL-18, cleavage of caspase-1, and induction of cell death. K+ efflux induced by N. caninum infection participated in the activation of the inflammasome. Infection of mice deficient in NLRP3, ASC, and caspase-1/11 resulted in decreased production of IL-18 and reduced IFN-γ in serum. Elevated numbers of monocytes/macrophages and neutrophils were found at the initial infection site, but they failed to limit N. caninum replication. These findings suggest that the NLRP3 inflammasome is involved in the host response to N. caninum infection at the acute stage and plays an important role in limiting parasite growth, and it may enhance Th1 response by inducing production of IFN-γ. These findings may help devise protocols for controlling neosporosis.

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“…Neosporosis is considered as one of the main infectious causes of abortion in cattle, as well as stillbirth and the birth of weak calves, leading to a significant economic burden on the beef and dairy industries worldwide [4]. Currently, neither effective vaccines nor drugs have been developed for the prevention and treatment of neosporosis due to the elusive anti-N. caninum immune mechanisms in the hosts [5,6]. Neospora caninum has three infectious stages (tachyzoites, bradyzoites and sporulated oocysts).…”

Section: Introductionmentioning

confidence: 99%

ROS-mediated NLRP3 inflammasome activation participates in the response against Neospora caninum infection

Wang

Gong

et al. 2020

Parasites Vectors

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Background: Neospora caninum is an obligate intracellular protozoan that causes neosporosis, N. caninum infection is a major cause of abortion in cattle worldwide. Currently, specific treatment for neosporosis is not available. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a cytoplasmic protein complex that plays an important role in host defense against N. caninum infection, but the underlying mechanisms are poorly understood. Methods: The reactive oxygen species (ROS) inhibitor and the ROS inducer, wild-type (WT) and NLRP3-deficient peritoneal macrophages or mice were used to investigate the role of ROS in NLRP3 inflammasome activation and controlling parasite burdens. ROS production, cell death and cell viability, production of inflammasome-mediated IL-1β or IL-18, cleavage of caspase-1 and NLRP3 expression, as well as parasite burdens were detected. Results: In vitro, N. caninum induced ROS generation in a dose-dependent manner in peritoneal macrophages. The pretreatment of ROS inhibitor N-acetyl-l-cysteine (NAC) significantly attenuated N. caninum-induced ROS production, LDH release, IL-1β secretion and NLRP3 expression, whereas N. caninum proliferation was notably increased. In contrary, the ROS inducer pyrogallol (PG) significantly enhanced ROS production and NLRP3 inflammasome activity and decreased the parasite burden in N. caninum-infected peritoneal macrophages. NADPH-dependent ROS-mediated NLRP3 inflammasome activation induced by N. caninum can also be confirmed by using the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). However, the NAC or DPI pre-treatment or PG treatment did not significantly alter N. caninum-induced inflammasome activities and parasite proliferation in Nlrp3 −/− peritoneal macrophages. In vivo, IL-18 releases in serum and parasite burdens in peritoneal exudate cells were significantly increased in PG-treated WT mice after infection with N. caninum; however, IL-18 productions and parasite burdens were not changed in PGtreated Nlrp3 −/− mice. Furthermore, PG treatment in WT mice infected with N. caninum significantly decreased the mortality, weight loss and parasite burdens in tissues and histopathological lesions. Conclusions: Neospora caninum-induced NADPH-dependent ROS generation plays an important role in NLRP3 inflammasome activation and controlling parasites. The ROS inducer PG can control N. caninum infection mainly by promoting NLRP3 inflammasome activation. ROS-mediated NLRP3 inflammasome axis can be a potential therapeutic target for neosporosis.

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Review on the immunological and molecular diagnosis of neosporosis (years 2011–2016)

Cited by 33 publications

References 85 publications

Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294

Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294

NLRP3 Inflammasome Participates in Host Response to Neospora caninum Infection

ROS-mediated NLRP3 inflammasome activation participates in the response against Neospora caninum infection

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