Interleukin-10 Limits Local and Body Cavity Inflammation during Infection with Muscle-StageTrichinella spiralis

Abstract

The aim of this study was to characterize cellular responses to muscle-stage Trichinella spiralis. From its intracellular habitat in muscle, T. spiralis secretes potent glycoprotein antigens that elicit a strong systemic host immune response. Despite the magnitude and prolonged nature of this response, nurse cells are rarely destroyed by infiltrating cells. We tested the hypothesis that the anti-inflammatory cytokine interleukin-10 (IL-10) moderates cellular responses to muscle-stage parasites. Trichinella larvae colonize the diaphragm in large numbers, prompting us to evaluate regional responses in body cavities in addition to local responses in muscle. Mice deficient in IL-10 demonstrated an exaggerated inflammatory response around nurse cells and in the pleural cavity. The effect of IL-10 was most evident 20 days following muscle infection. The increased intensity of the response in IL-10-deficient mice did not affect parasite establishment or survival. Between 20 and 50 days postinfection, the inflammatory response was diminished in both wild-type and IL-10-deficient mice. Muscle infection also elicited an antibody response, characterized initially by mixed isotypes directed at somatic larval antigens and changing to an immunoglobulin G1-dominated response directed at tyvelosebearing excreted or secreted antigens. We conclude that IL-10 limits local and regional inflammation during the early stages of muscle infection but that chronic inflammation is controlled by an IL-10-independent mechanism that is coincident with a Th2 response.

In vivo inhibition of inducible nitric oxide synthase by aminoguanidine influences free radicals production and macrophage activity in Trichinella spiralis infected low responders (C57BL/6) and high responders (BALB/c) mice

“…Other studies showed higher IFN-γ level and lower IL-5 level after 15 dpi in BALB/c mice infected with T. spiralis, what additionally confirms the role of Th-1 response (Dvorožňáková et al, 2005). Cytotoxic activation of macrophages was also suggested by Beiting et al (2004) who demonstrated IL-10 participation in local inflammatory response suppression in the neighborhood of nurse-cell as well as studies where revealed strong growth of antioxidant enzymes (ex. superoxide dismutase (SOD)) level in blood and muscles (Derda & Hadaś, 2000;Derda et al, 2004).…”

Expulsion of Secondary Trichinella spiralis Infection in Rats Occurs Independently of Mucosal Mast Cell Release of Mast Cell Protease II

“…Although we did not detect the obvious cellular changes in the intestines of rats infected by this route, it is possible for stimulation of mucosal associated lymphoid tissue in one site to affect another site. An additional source of cellular mediators may derive from the body cavities in which cellular expansion during muscle infection has been documented in mice (52,53). Recirculation of cells from the cavities to the intestinal tract, or direct effects of peritoneal responses on the gut have been shown to be a part of the body's defense against intestinal pathogens (54).…”

Differences in cellular immune responses of mice BALB/c to low and high infective doses of Trichinella spiralis

“…Also during the muscle phase of the light infection there was an increased occurrence of CD4 cells in comparison with the heavy infection. The increase of both T cell populations during the muscle phase of trichinellosis can be associated with larval development in nurse cells, which are surrounded by macrophages, CD8+ and CD4+ T lymphocytes and B lymphocytes (Beiting et al, 2004). Cytokines synthetized primarily by T helper cells play a dominant role in orchestrating both anti-parasite responses and pathology in many helminth infections including trichinellosis (Finkelman et al 1997).…”

“…Larvae survive in nurse cells in close association with macrophages, CD8+ and CD4+ T lymphocytes, and B lymphocytes. B lymphocytes secreting antibodies, particularly IgG and IgE, may lead to an effective antibodydependent cell mediated cytotoxic reaction against newborn larvae (Beiting et al, 2004). Potential differences in a development of the host immune HELMINTHOLOGIA, 50, 4: 244 -253, 2013 Differences in cellular immune responses of mice BALB/c to low and high infective doses of Trichinella spiralis 245 response to different infective doses of Trichinella and host-parasite interactions are rarely studied.…”