University of Massachusetts Medical School Faculty Publications

Title

Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

1-16-2013

Document Type

Article

Disciplines

Immunity | Immunology of Infectious Disease | Molecular Genetics | Parasitic Diseases

Abstract

"Triple-defective" (3d) mice carrying a mutation in UNC93B1, a chaperone for the endosomal nucleic acid-sensing (NAS) Toll-like receptors TLR3, TLR7, and TLR9, are highly susceptible to Toxoplasma gondii infection. However, none of the single or even the triple NAS-TLR-deficient animals recapitulated the 3d susceptible phenotype to experimental toxoplasmosis. Investigating this further, we found that while parasite RNA and DNA activate innate immune responses via TLR7 and TLR9, TLR11 and TLR12 working as heterodimers are required for sensing and responding to Toxoplasma profilin. Consequently, the triple TLR7/TLR9/TLR11-deficient mice are highly susceptible to T. gondii infection, recapitulating the phenotype of 3d mice. Humans lack functional TLR11 and TLR12 genes. Consistently, human cells produce high levels of proinflammatory cytokines in response to parasite-derived RNA and DNA, but not to Toxoplasma profilin, supporting a more critical role for NAS-TLRs in human toxoplasmosis.

Rights and Permissions

Citation: Cell Host Microbe. 2013 Jan 16;13(1):42-53. doi: 10.1016/j.chom.2012.12.003. Link to article on publisher's site

Related Resources

Link to Article in PubMed