Trichinella spiralis Secreted Enzymes Regulate Nucleotide-Induced Mast Cell Activation and Release of Mouse Mast Cell Protease 1

Abstract

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.

Mucosal Mast Cells Response in the Jejunum of Ascaridia galli-Infected Laying Hens

“…Anthony et al (2007) explained that many of effector cells are acti�ated in response to most helminth infections including mast cells. Mucosal mast cells contribute to expulsion of a number of gastrointestinal nematode parasites (Afferson et al, 2012).…”

“…Currently, little information is a�ailable describing the effects of A. galli infection on the mucosal defense regarding mast cells response of small jejunal of laying hens. Reference to mucosal mast cells mediate Trichinella spiralis, the nematode resides within enterocytes of the jejunum, expulsion from the intestine of mice has been reported (Ierna et al, 2005;Suzuki et al, 2008;Afferson et al, 2012); howe�er, De-yuan et al (2003) reported that the mucosal mast cells in jejunum of chickens infected with A. galli were increased with no significantly difference but a remarkable decrease of mast cells in the thymic medulla. Thus, the aim of the current study was to in�estigate the effects of A. galli infection on the mucosal defense based on mucosal mast cells response in jejunal of laying hens.…”

Oral contraceptive pills: Risky or protective in case of Trichinella spiralis infection?

“…During the enteral phase of trichinellosis, a huge amount of nucleotides are released from damaged tissue. As these free nucleotides stimulate the immune system, T. spiralis worms start to secrete a range of nucleotide‐metabolizing enzymes to decrease the released nucleotides and promote an anti‐inflammatory environment . Interestingly, some recent evidences indicate that recruited mast cells participate in controlling the inflammatory status by enhancing the tissue remodelling process after injury.…”

Mast cells: new therapeutic target in helminth immune modulation

“…T. spiralis‐ secreted molecules have also been shown to selectively modulate the secretion profiles of activated mast cells while T. spiralis muscle larval antigens were demonstrated to induce the release of histamine but inhibit β‐hexosaminidase in mast cells . T. spiralis‐ secreted enzymes were also shown to inhibit mouse mast cell protease 1 .…”