A role of peptidoglycan recognition proteins in regulating innate immune response

Abstract

By now, a whole number of pathogenic antibiotic-resistant or tolerant microorganisms has been progressively increased. Hence, efficient fight against them requires to change the class of antibiotics, increase their dose, or develop new antimicrobial drugs. On the contrary, another option could rely on augmenting innate immunity. During coevolution, eukaryotes have developed several ways for their protection against microorganisms. Innate immunity conserved in all multicellular organisms. The essential principles of innate immunity include recognition of a foreign structures and their subsequent destruction. A set of specific receptors recognize conserved pathogen-derived structures. Elimination occurs due to phagocytosis and cleavage, e.g. via oxidative burst in phagocytic cells, compliment system or antimicrobial peptides. Recognition system in innate immunity is based on the pattern recognition receptors. Due to the pathogen diversity, multiple conserved structures typical to pathogens (e.g. lipopolysaccharide, peptidoglycan, flagellin etc.) are sensed by numerous receptors. The family of peptidoglycan recognition proteins is among such receptors, which were first isolated in 1996 from the silkworm Bombyx mori and mice. Later, it was demonstrated that this family is conserved and its members are found in insects, fish and mammals. Here, functions of insect peptidoglycan recognition proteins in Drosophila melanogaster as well as mammals are discussed. Such proteins are expressed mainly in liver cells (insects — in adipose tissue cells as analogue of mammalian liver), intestinal cells, and epidermis. Numerous studies demonstrate that peptidoglycan-recognition proteins moderate immune response, and may act as antimicrobial proteins, or to regulate microbiota as well as prevent enterocyte activation and restrict inflammatory response. Due to evolutionary conservatism observed for such proteins and inability for bacteria to evade their protective effects, it seems promising to use peptidoglycan recognition proteins in a combination therapeutic approach against antibiotic-resistant and antibiotic-tolerant forms of microorganisms.

Keywords

• innate immunity
• peptidoglycan recognition proteins
• pgrp
• pglyrp
• pattern-recognition receptors
• drosophila melanogaster
• immune response