NLR proteins and parasitic disease

Abstract

Parasitic diseases are a serious global health concern. Many of the most common and most severe parasitic diseases, including Chagas’ disease, leishmaniasis, and schistosomiasis, are also classified as neglected tropical diseases and are comparatively less studied than infectious diseases prevalent in high income nations. The NLRs (nucleotide-binding domain leucine-rich-repeat-containing proteins) are cytosolic proteins known to be involved in pathogen detection and host response. The role of NLRs in the host response to parasitic infection is just beginning to be understood. The NLR proteins NOD1 and NOD2 have been shown to contribute to immune responses during Trypanosoma cruzi infection, Toxoplasma gondii infection, and murine cerebral malaria. The NLRP3 inflammasome is activated by T. cruzi and Leishmania amazonensis but also induces pathology during infection with schistosomes or malaria. Both the NLRP1 and NLRP3 inflammasomes respond to T. gondii infection. The NLRs may play crucial roles in human immune responses during parasitic infection, usually acting as innate immune sensors and driving the inflammatory response against invading parasites. However, this inflammatory response can either kill the invading parasite or be responsible for destructive pathology. Therefore, understanding the role of the NLR proteins will be critical to understanding the host defense against parasites as well as the fine balance between homeostasis and parasitic disease.

Proteomic analysis of host brain components that bind to infectious particles in Creutzfeldt‐Jakob disease

“…However, an approximately threefold increase in the anion transporter B3AT, an AD and senescence marker was observed. The 2.5‐fold increase in the cytosolic leucine rich repeat LRC59 that binds polyA RNA is also involved in pathogen detection . In sum, most of the proteins in less purified FU‐CJD p18 particles represent host pathologic responses and disease markers.…”

Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition

“…Recent studies have further identified a critical role for the NLRP3 inflammasome in the host response to several viral and parasitic pathogens such as West Nile virus, Dengue virus, Trypanosoma cruzi and malaria (reviewed3233). Importantly, the function and role of the NLRP3 inflammasome was characterized by use of gene-deficient mice.…”

Evasion of inflammasome activation by microbial pathogens

“…As such, a wide array of agonists are capable of activating the NLRP3 inflammasome, including those derived from microbes (PAMPs) or from endogenous or environmental sources (DAMPs) (20). Microbial activators of the NLRP3 inflammasome include both Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Listeria monocytogenes, Streptococcus pneumoniae, Neisseria gonorrhoeae, and others) (21), fungi (Candida albicans, Aspergillus fumigatus, Microsporum canis, and others) (22), RNA and DNA viruses (influenza virus, adenovirus, respiratory syncytial virus [RSV], and others) (23), and parasitic pathogens (Plasmodium chabaudi, Leishmania amazonensis, and Schistosoma mansoni) (24). Given the large number of chemically and structurally diverse agonists that are capable of activating the NLRP3 inflammasome, it is unlikely that NLRP3 directly Figure 1.…”