Toll-like receptor 11

Toll-like receptor 11 (TLR11) is a protein that in humans is encoded by the TLR11 gene. TLR11 belongs to the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. The significance of TLR11 in humans is limited due to a pseudogene formation, but it is functionally active in mice and other animals, where it recognizes protozoan parasites and potentially other pathogens.

Function

TLR11 is involved in the innate immune response to microbial agents. In mice, TLR11 recognizes and is activated by profilin-like molecules from protozoans such as Toxoplasma gondii, and possibly by other pathogens. Upon recognition of its ligands, TLR11 initiates a signaling cascade that results in the activation of nuclear factor kappa B (NF-κB), leading to the production of pro-inflammatory cytokines and chemokines. This response is crucial for the host's defense against infections. However, the exact role and ligands of TLR11 in humans remain speculative due to its pseudogene status, which suggests that it is not functional in the human immune response.

Genetic and Evolutionary Aspects

The TLR11 gene is located on chromosome 12 in mice, where it encodes a protein of approximately 1000 amino acids. In humans, due to a frame-shift mutation, the TLR11 gene does not produce a functional protein and is considered a pseudogene. This mutation is thought to have occurred relatively recently in human evolution, suggesting that TLR11 may have been functional in the ancestors of modern humans. The evolutionary loss of TLR11 function in humans raises questions about the redundancy and adaptability of the immune system, as well as the potential for other TLRs to compensate for its absence.

Clinical Significance

While TLR11 is not functional in humans, its study in animal models, particularly mice, provides valuable insights into the immune response to certain pathogens, especially those that are not well recognized by other TLRs. Understanding the signaling pathways and immune responses mediated by TLR11 can contribute to the development of vaccines and therapeutic agents against infections caused by protozoan parasites and potentially other pathogens. Additionally, research on TLR11 and its ligands may offer clues about the evolutionary pressures that have shaped the human immune system and the functional redundancy within the TLR family.

See Also

• Toll-like receptor
• Innate immune system
• Toxoplasma gondii
• Cytokine
• Nuclear factor kappa B

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