Trichinella spiralis secreted enzymes regulate nucleotide-induced mast cell activation and release of mouse mast cell protease 1.
Extracellular nucleotides are important triggers of innate immunity, acting on a wide variety of cells via signaling through purinergic receptors. Mucosal mast cells contribute to expulsion of a number of gastrointestinal nematode parasites, and mouse mast cell protease 1 has been shown to have a critical role in clearance of Trichinella spiralis from the intestinal tract. We show here that adenosine, ADP, ATP, UDP, and UTP all stimulate calcium mobilization in bone marrow-derived mast cells with a mucosal phenotype. Secreted proteins from T. spiralis infective larvae inhibit nucleotide-induced mast cell activation, and that induced by ADP and UDP is specifically blocked by parasite secretory 5'-nucleotidase. Release of mouse mast cell protease 1 is stimulated by ADP and ATP. Both parasite secreted products and the 5'-nucleotidase inhibit ADP-induced release of mast cell protease, whereas that stimulated by ATP is partially inhibited by secreted products alone. This indicates that the 5'-nucleotidase contributes to but is not solely responsible for inhibition of nucleotide-mediated effects on mast cell function. Secretion of nucleotide-metabolizing enzymes by parasitic nematodes most likely evolved as a strategy for suppression of innate immune responses and is discussed in this context.
Department of Life Sciences, Imperial College London, London, United Kingdom.
Holly C
HC
Afferson
Emily
E
Eleftheriou
Murray E
ME
Selkirk
Kleoniki
K
Gounaris
D000818:Animals; D002478:Cells, Cultured; D053818:Chymases / Q000096:biosynthesis*; D016207:Cytokines / Q000378:metabolism; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D009711:Nucleotides / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017160:Trichinella spiralis / Q000201:enzymology* / Q000276:immunology / Q000502:physiology; D014235:Trichinellosis / Q000276:immunology*
D016207:Cytokines; D009711:Nucleotides; D053818:Chymases; C509230:Mcpt1 protein, mouse