Combined Action of Nucleic Acid-Sensing Toll-like Receptors and TLR11/TLR12 Heterodimers Imparts Resistance to Toxoplasma gondii in Mice

Warrison A. Andrade et al,. Cell Host & Microbe 2013, 13:1-12

Speaker: Chiung-Chen Chou (周炯呈)                 Time: 15:10~16:00, March 6, 2013

Commentator: Dr. Ping Lin (凌斌 老師)             Place: Room 601

Abstract

Toxoplasma gondii is protozoa parasite that has been described in more than 300 mammals. Mice are the intermediate host in the life cycle of T. gondii, and cats are definitive host. Humans infected by T. gondii are thought to be “accidental” intermediate hosts which carried a chronic disease called toxoplosmosis. It can establish chronic infection and is characterized by the formation of tissue cysts in the brain. The cysts keep on largely quiescent for the life of the host, but it can reactivate and cause life-threatening toxoplasmic encephalitis in immunocompromised patients, such as those with neoplastic diseases and organ transplants. “Triple-defective” (3d) mice carrying a mutant in UNC93B1 which affect nucleic acid-sensing (NAS) Toll-like receptors (TLR) TLR3, TLR7, TLR9, are susceptible to T. gondii. The mammalian homolog B1 of Caenorhabditis elegans known as UNC93B1 is a chaperone protein that mediates translocation of the nucleic acid-sensing Toll-like receptors (TLRs) from the endoplasmic reticulum (ER) to the endolysosomes [1]. But none of NAS-TLR-deficient mice model had 3d susceptible phenotype. The author found the RNA and DNA derived from T. gondii tachyzoites activate host innate immunity via TLR7 and TLR9. TLR11 and TLR12 worked as a heterodimer and response to T. gondii profilin-like protein (TgPRF). TLR7/TLR9/TLR11-deficient mice are susceptible to parasitic infection as same phenotype of 3d mice to experimental toxoplasmosis. Hence, human infected by T. gondii produce immune cytokine to parasite’s RNA and DNA, indicating that NAS-TLRs have an important role in human toxoplasmosis.

References

1.      Bruno Luiz Fonseca Schamber-Reis, et al. UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major. J Bio Chem. 2013

2.      K. Tabeta, et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat Immunol 2006, 7:156-164