Functional aspects of Toll-like receptor/MyD88 signalling during protozoan infection: focus on Toxoplasma gondii

Abstract

Toll-like receptor (TLR)/MyD88 signalling has emerged as a major pathway of pathogen recognition in the innate immune system. Here, we review recent data that begin to show how this pathway controls the immune response to protozoan infection, with particular emphasis on the opportunistic pathogen Toxoplasma gondii. The various ways that the parasite activates and suppresses TLR/MyD88 signalling defines several key principals that illuminate the complexities of the host-pathogen interaction. We also speculate how TLR/MyD88 signalling might be exploited to provide protection against Toxoplasma, as well as other protozoa and infection in general.

Fig. 1

Alternative models for the role of MyD88 in immunity to infection. (a) MyD88 signalling as a bridge to acquired immunity. After pathogen internalization through either active invasion or phagocytosis by a dendritic cell, microbial peptides are displayed on the cell surface in association with major histocompatibility complex (MHC) class II molecules. At the same time, pathogen-associated Toll-like receptor (TLR) ligands trigger proinflammatory cytokine and co-stimulatory expression on the dendritic cell. The combined stimuli trigger activation and differentiation of T cells specific for the antigenic peptide, resulting in some cases to an immunodominant T cell response. (b) Some studies suggest that T lymphocyte activation proceeds independently of MyD88, and that other pathogen-triggered factors provide signals for T cell differentiation (blue arrows). MyD88 is still important in the response to infection (black arrows), but its function is relegated to signalling pathways that lead to innate anti-microbial control of infection, allowing host survival until development of adaptive immunity. Which of these models predominates may depend on the nature of the pathogen, the particular cell type involved or the route of infection. In principle, it is possible that both pathways operate simultaneously in the host response to infection.