Abstract
BackgroundNeospora caninum is an intracellular parasite that causes significant economic losses in cattle industry. Understanding the host resistance mechanisms in the innate immune response to neosporosis could facilitate the exploration of approaches for controlling N. caninum infection. The NLR inflammasome is a multiprotein platform in the cell cytoplasm and plays critical roles in the host response against microbes.MethodsNeospora caninum-infected wild-type (WT) macrophages and Nlrp3−/− macrophages, and inhibitory approaches were used to investigate inflammasome activation and its role in N. caninum infection. Inflammasome RT Profiler PCR Arrays were used to identify the primary genes involved in N. caninum infection. The expression of the sensor protein NLRP3, processing of caspase-1, secretion of IL-1β and cell death were detected. Neospora caninum replication in macrophages was also assessed.ResultsMany NLR molecules participated in the recognition of N. caninum, especially the sensor protein NLRP3, and further study revealed that the NLRP3 distribution became punctate in the cell cytoplasm, which facilitated inflammasome activation. Inflammasome activation-mediated caspase-1 processing and IL-1β cleavage in response to N. caninum infection were observed and were correlated with the time of infection and number of infecting parasites. LDH-related cell death was also observed, and this death was regarded as beneficial for the clearance of N. caninum. Treatment of N. caninum-infected macrophages with caspase-1, pan-caspase and NLRP3 inhibitors led to the impaired release of active IL-1β and a failure to restrict parasite replication. And Neospora caninum infected peritoneal macrophages from Nlrp3-deficient mice displayed greatly decreased release of active IL-1β and the failure of caspase-1 cleavage.ConclusionsThe NLRP3 inflammasome can be activated in N. caninum-infected macrophages, and plays a protective role in the host response to control N. caninum.
Highlights
Neospora caninum is an intracellular parasite that causes significant economic losses in cattle industry
The MEFV (FMF/TRIM20), TNF (TNF-α), TNFSF11 (Ly109l/ODF), and TNFSF4 (Ath1/CD134L) genes were upregulated at both 12 and 24 h p.i. (Fig. 1c). These results indicate that many types of genes in the inflammasome pathway participated in the response to N. caninum infection, several receptor genes are upregulated, and NLRP3 is the most upregulated sensor protein
The data demonstrated that several sensor molecules, especially NLRP3, were upregulated in Peritoneal macrophages (PMs) infected with N. caninum without LPS priming because the NF-κB pathway can be activated by N. caninum through TLR3 [5], TLR2 [9] and NOD2 [7]
Summary
Neospora caninum is an intracellular parasite that causes significant economic losses in cattle industry. Understanding the host resistance mechanisms in the innate immune response to neosporosis could facilitate the exploration of approaches for controlling N. caninum infection. A good understanding of the immune mechanisms that mediate host resistance to neosporosis may facilitate the discovery of approaches to control neosporosis. As it is an intracellular parasite, the intracellular proliferation of N. caninum tachyzoites is a key step in the pathogenesis of neosporosis. The innate immune system is the first line of defense in host resistance to N. caninum infection, playing an important role in the control of the initial parasite replication and mediating an appropriate adaptive immune response [7]. Studies show that TLR2 [9] and TLR3 [5], which belong to the Toll-like receptors (TLRs) family, participate in the initial recognition of N. caninum, induce the secretion of the pro-inflammatory cytokines IL-12 and IFN-γ, and mediate the immune response against N. caninum
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
