Location: Animal Parasitic Diseases LaboratoryTitle: Myeloid derived suppressor cells enhance IgE-mediated mast cell responses) Author
Submitted to: Journal of Leukocyte Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/2013
Publication Date: 4/1/2014
Citation: Morales, J.K., Saleem, S.J., Martin, R.K., Barnstein, B.O., Graham, L., Bear, H.D., Urban Jr, J.F., Conrad, D.H., Ryan, J.J. 2014. Myeloid derived suppressor cells enhance IgE-mediated mast cell responses. Journal of Leukocyte Biology. 95(4):643-650 DOI: 10.1189/jlb.0913510. Interpretive Summary: The host response to parasitic nematode infection is complex. Protective immunity to eliminate the parasite may have a negative cost to the host because of the level of inflammation and tissue destruction that accompany the protective response. It is important to understand the host protective mechanism in order to establish a resistance to the infection without undue harm to the host. We demonstrated that a specialized cell found in the bone marrow of mice called myeloid derived suppressor cells (MDSC) can enhance the activity of mast cells that interact with an antibody class called IgE to expel the nematode parasite Trichinella spiralis which is a food safety concern because it can infect humans when edible animal tissues have the worm parasite. Notably, eliminating the MDSC will lower tissue inflammation, but it also reduces the level of protection against the worm. These data support the hypothesis that MDSC enhance the mast cell inflammatory response, promoting both protective and pathological outcomes. This information is not only important for scientists to understand how to control protection against worm parasites, but mast cell responses are critical to the intensity of allergic disease and thus can help limit the level of inflammation in humans with allergy. The study, therefore, has benefit to both those interested in controlling parasitic infection in livestock and allergic disease in humans.
Technical Abstract: We previously demonstrated that enhanced development of myeloid derived suppressor cells (MDSC) in ADAM10 transgenic mice yielded resistance to infection with Nippostrongylus brasiliensis infection, and that co-culturing MDSC with IgE-activated mast cells enhanced cytokine production. In the current work we show that MDSC enhance the mast cell response to IgE. Both Ly6C+ and Ly6C/G doublepositive MDSC subsets enhanced IgE-induced mast cell cytokine and chemokine production. These interactions were functionally important, since MDSC depletion with the FDA-approved drug gemcitabine exacerbated infection with Nippostrongylus brasiliensis or Trichinella spiralis, and reduced mast cell-dependent airway hyper-responsiveness (AHR) and lung inflammation. Adoptive transfer of MDSC worsened AHR in wild type, but not mast cell-deficient Wsh/Wsh mice. These data support the hypothesis that MDSC enhance the mast cell inflammatory response, promoting both protective and pathological outcomes.