Glycoconjugates of Gram-negative bacteria and parasitic protozoa – are they similar in orchestrating the innate immune response?

Abstract

Innate immunity is an evolutionarily ancient form of host defense that serves to limit infection. The invading microorganisms are detected by the innate immune system through germline-encoded PRRs. Different classes of PRRs, including TLRs and cytoplasmic receptors, recognize distinct microbial components known collectively as PAMPs. Ligation of PAMPs with receptors triggers intracellular signaling cascades, activating defense mechanisms. Despite the fact that Gram-negative bacteria and parasitic protozoa are phylogenetically distant organisms, they express glycoconjugates, namely bacterial LPS and protozoan GPI-anchored glycolipids, which share many structural and functional similarities. By activating/deactivating MAPK signaling and NF-κB, these ligands trigger general pro-/anti-inflammatory responses depending on the related patterns. They also use conservative strategies to subvert cell-autonomous defense systems of specialized immune cells. Signals triggered by Gram-negative bacteria and parasitic protozoa can interfere with host homeostasis and, depending on the type of microorganism, lead to hypersensitivity or silencing of the immune response. Activation of professional immune cells, through a ligand which triggers the opposite effect (antagonist versus agonist) appears to be a promising solution to restoring the immune balance.