|Mcconchie, B - NIAID/NIH ROCKVILLE MD|
|Norris, H - NIAID/NIH ROCKVILLE MD|
|Bundoc, V - NIAID/NIH ROCKVILLE MD|
|Trivedi, Shweta - NIAID/NIH ROCKVILLE MD|
|Boesen, Agnieszka - NIAID/NIH ROCKVILLE MD|
|Keane-Myers, A - NIAID/NIH ROCKVILLE MD|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 15, 2006
Publication Date: December 1, 2006
Citation: McConchie, B.W., Norris, H.H., Bundoc, V.G., Trivedi, S., Boesen, A., Urban Jr, J.F., Keane-Myers, A.M. 2006. Ascaris suum-derived products suppress mucosal allergic inflammation in an interleukin-10-independent manner via interference with dendritic cell function. Infection and Immunity. 74(12):6632-6641. Interpretive Summary: Disease interactions are often studied in mice because of the availability of reagents that can define both genetic and immunological characteristics of this species. Hypothesis-based testing of complex disease interactions are facilitated by the use of these models. The current study describes the evaluation of a product derived from the parasitic large round worm of swine, Ascaris suum that suppresses immune responses to defined antigens and allergens. This test system provides a convenient screening tool to determine the biological activity of parasite-derived products on immune and inflammatory processes. The hypothesis that was tested was that the worm infection both stimulates and suppresses components of the immune system that contribute to parasitic disease and also affect secondary responses to non-parasite antigens. In fact, it was observed that while a worm infection enhanced the allergic response to ragweed, multiple infections suppressed the response to background levels. This observation was repeated using a product derived from adult Ascaris that suppressed responses to both ragweed and albumin proteins. The model is useful because it provides a molecular basis to the observation of immune suppression by parasites and targets specific cell populations in the host that are involved in the processing and presentation of antigens to induce immune activation. This observation can now be tested in host species economic interest such as swine. This technology will be helpful to members of the scientific community that test substance with immune modulating activity that can be used to appropriately regulate immune function in livestock and man.
Technical Abstract: We have previously shown an inverse relationship between chronic helminth infection with Ascaris suum and protection from allergic inflammation. This helminth-mediated protection was characterized by a global increase in IL-10 and the development of protective CD4+/CD25+ T cells. Here, we used A. suum pseudocoelomic fluid (PCF) in lieu of infection to define molecular mechanisms of allergic protection in a mouse model of allergic inflammation. Mice were sensitized with ragweed (RW) and PCF (RW/PCF), PCF alone, or RW alone, and challenged intratracheally, intranasally, and supra-ocularly with RW. Histological examination of the eyes and lungs, analysis of the bronchoalveolar lavage (BAL), and characterization of ex vivo cytokine responses in these mice were performed to determine allergic inflammatory responses. RW/PCF-treated mice had suppressed allergic immune responses compared to mice given RW alone. To investigate whether IL-10 was involved in PCF-mediated allergic protection, we tested mice genetically deficient of IL-10. Persistent protection from allergic disease was observed in the absence of IL-10, indicating the primary mechanism of PCF protection is IL-10-independent. Finally, PCF-treated dendritic cells (DC) had reduced activation receptor expression and cytokine production in response to either RW or LPS stimulation. These findings extend previous studies that showed that infection with A. suum alters expression of allergic disease, and suggest that PCF can contribute to this effect by interference with DC function.