What is the Difference Between Toll-Like Receptors and Nod-Like Receptors

The key difference between Toll-like receptors and Nod-like receptors is that Toll-like receptors are membrane-bound proteins that play a key role in microbial identification in the innate immune system, while Nod-like receptors are proteins present in the cytoplasm that play a key role in microbial identification in the innate immune system.

The innate immune system uses a wide variety of receptors to recognize and respond to microbial pathogens. These receptors bind to repeating patterns such as carbohydrate or lipid moieties present in microbial surfaces in order to trigger innate immune responses. Their function contributes to the onset of adaptive immunity. Toll-like receptors and Nod-like receptors are two different types of receptors working in the innate immunity system.

CONTENTS

1. Overview and Key Difference
2. What are Toll-Like Receptors 
3. What are Nod-Like Receptors
4. Similarities – Toll-Like Receptors and Nod-Like Receptors
5. Toll-Like Receptors vs Nod-Like Receptors in Tabular Form
6. Summary – Toll-Like Receptors vs Nod-Like Receptors

What are Toll-Like Receptors?

Toll-like receptors (TLRs) are membrane-bound proteins that play a key role in microbial identification in the innate immune system. They are single-pass membrane-spanning receptors. Generally, these receptors are expressed by sentinel cells such as macrophages and dendritic cells. When microbes breach physical barriers like the skin or intestinal mucosa, they are recognized by these membrane-bound receptors in order to activate immune responses. The TLRs members include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans do not possess genes for TLR11, TLR12, and TLR13, while mice do not possess a functional gene for TLR10. Moreover, TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles. TLR3, TLR7, TLR8, and TLR9 receptors are sensors of nucleic acids.

Figure 01: Toll-Like Receptors

TLRs received their name due to their similarity to the protein encoded by the toll gene. Upon activation, these receptors ultimately lead to the upregulation or suppression of genes that orchestrate inflammatory responses and other transcriptional events. Some of these important events lead to cytokine production, proliferation, and survival. On the other hand, other events lead to greater adaptive immunity. Furthermore, medically certain drugs (imiquimod, resiquimod) called TLR agonists (TLR7 & TLR8) have been explored in cancer immunotherapy. TLR ligands are in clinical development as vaccine adjuvants.

What are Nod-Like Receptors?

Nod-like receptors (NLRs) are proteins present in the cytoplasm and play a key role in microbial identification in the innate immune system. They are also called nucleotide-binding oligomerization domain-like receptors. They are intracellular sensors. These receptors identify pathogen-associated molecular patterns (PAMPS) that enter the cell via phagocytosis or pores and damaged associated molecular patterns (DAMPs) that are associated with cell stress. NLRs are divided into 4 subfamilies based on the type of N terminal domain: NLRA, NLRB, NLRC, and NLRP. There is also an additional subfamily called NLRX, which does not have significant homology to any N terminal domain. Moreover, NLRs can be divided into 3 subfamilies based on their phylogenetic relationships, such as NODs, NLRPs, and IPAF.

Figure 02: Nod-Like Receptors

NLRs can cooperate with TLRs and regulate inflammatory and apoptotic responses. Furthermore, their homologs have been identified in different animal species (APAF1). These homologs are also discovered in the plant kingdom (disease resistance R protein).

What are the Similarities Between Toll-Like Receptors and Nod-Like Receptors?

• Toll-like receptors and Nod-like receptors are two different types of receptors in the innate immunity system.
• Both receptors are proteins made up of amino acids.
• These receptors can cooperate with each other to regulate inflammatory and apoptotic responses.
• Both receptors are highly conserved through evolution.
• These receptors contain leucine-rich repeats.
• They contribute to the onset of adaptive immunity.

What is the Difference Between Toll-Like Receptors and Nod-Like Receptors?

Toll-like receptors are membrane-bound proteins that play a key role in microbial identification in the innate immune system, while Nod-like receptors are proteins present in the cytoplasm that play a key role in microbial identification in the innate immune system. Thus, this is the key difference between Toll-like receptors and Nod-like receptors. Furthermore, Toll-like receptors are extracellular sensors of pathogen-associated molecular patterns (PAMPs). On the other hand, Nod-like receptors are intracellular sensors of pathogen-associated molecular patterns (PAMPs).

The below infographic presents the differences between Toll-like receptors and Nod-like receptors in tabular form for side by side comparison.

Summary – Toll-Like Receptors vs Nod-Like Receptors

Toll-like receptors and Nod-like receptors are two different types of receptors in the innate immunity system. Both receptors are sensors of pathogen-associated molecular patterns (PAMPs). Toll-like receptors are membrane-bound proteins while Nod-like receptors are proteins present in the cytoplasm. So, this is the key difference between Toll-like receptors and Nod-like receptors.

Reference:

1. “Toll like Receptor.” An Overview | ScienceDirect Topics.
2. “NOD-like Receptor.” An Overview | ScienceDirect Topics.

Image Courtesy:

1. “Toll like receptors” By BQUB1819-MBallve – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “Familias de PRRs” By Virtualf7.0 – Own work (CC BY-SA 4.0) via Commons Wikimedia

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