Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism

Abstract

Toll-like receptors (TLRs) have emerged as a major receptor family involved in non-self recognition. They have a vital role in triggering innate immunity and orchestrate the acquired immune response during bacterial and viral infection. However, the role of TLRs during infection with protozoan pathogens is less clear. Nevertheless, our understanding of how these parasitic microorganisms engage the host TLR signalling system has now entered a phase of rapid expansion. This Review describes recent insights into how parasitic protozoans are sensed by TLR molecules, and how the TLR system itself can be targeted by these microbial pathogens for their own survival.

Intraspecies Variation in Trypanosoma cruzi GPI-Mucins: Biological Activities and Differential Expression of α-Galactosyl Residues

“…15,[22][23][24][25]53 Extensive studies have reported on the biological activities of GPI-mucins from Y strain trypomastigotes, especially in the induction of NO and proinflammatory cytokines (IL-12 and TNF-α) by macrophages. 16,31,37 Furthermore, the molecular mechanisms of this induction were reported to involve members of the nuclear factor κB (NF-κB) pathway, including TLR2/TLR6, 17,18 MyD88, 54 extracellular signal-related (ERK) -1/ERK2 kinases, mitogen-activated protein kinase (MAPK), stress-activated protein kinase (SAPK-2/p38), and inhibitor of κB (IκB). 55,56 However, an unknown aspect of T. cruzi glycobiology is how tGPI-mucins from different strains/DTUs would trigger different responses in murine macrophages.…”

“…Finally, a heterodimer composed by Toll-like receptor 2 (TLR2) and TLR6 is involved in the recognition of T. cruzi tGPI-mucins. 17,18 Biochemically, the GPI moiety of T. cruzi mucins has the conserved core of Manα1-2Manα1-2Manα1-6Manα1-4GlcNα1-6myo-inositol-1-HPO 4 , which can be extended by phosphorylated substituents, including ethanolaminephosphate (EtNP), 2-aminoethylphosphonate (2-AEP), and extra carbohydrate residues. The EtNP or 2-AEP group serves as the point of attachment for the surface mucin glycoprotein moiety ( Figure 1).…”

Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell

“…17,18 Toll-like receptors (TLRs), for recognition of the pathogen-associated molecular pattern, are widely explored in innate and adaptive immune system. 19 CpG ODN primarily stimulates cells that express TLR9 including dendritic cells, monocytes and macrophages. However, some research reported that functional TLRs were also detected on tumor cells.…”

A central role for free heme in the pathogenesis of severe malaria: the missing link?

“…As for other infectious agents, Plasmodium expresses pathogen-associated molecular patterns (PAMP) that can be recognized by host germline-encoded pattern recognition receptors (PRR; reviewed in [10]). These signal in innate immune cells, such as monocyte/macrophages (Mø), to elicit a potent pro-inflammatory response.…”