NLRP3 Inflammasome Activation in Murine Macrophages Caused by Neospora Caninum Infection

Overview

Journal Parasit Vectors

Publisher Biomed Central

Specialties Parasitology
Tropical Medicine

Date 2017 Jun 1

PMID 28558839

Citations 20

Authors

Xiaocen Wang

Pengtao Gong

Xu Zhang

Jielin Wang

Lixin Tai

Xu Wang

Zhengkai Wei

Yongjun Yang

Zhengtao Yang

Jianhua Li

Xichen Zhang

Affiliations

Soon will be listed here.

Abstract

Background: 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. The NLR inflammasome is a multiprotein platform in the cell cytoplasm and plays critical roles in the host response against microbes.

Methods: Neospora 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.

Results: Many 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.

Conclusions: The NLRP3 inflammasome can be activated in N. caninum-infected macrophages, and plays a protective role in the host response to control N. caninum.

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