Salmonella enterica serovar Enteritidis is the major zoonotic and intracellular pathogen. Different strategies have been developed to prevent the S. Enteritidis infection. The beta-1,3-1,6-glucan of Schizophyllum commune was used as an immunological booster to determine the minimal dietary level of beta-glucan that would restrict S. Enteritidis infection through the effects of beta-glucan on the activity of macrophages and direct physical protection of the intestine. One-day-old male Single Comb White Leghorn chicks were used in all trials. In trials 1 and 2, the 0.1% beta-1,3-1,6-glucan treatment completely eliminated the viable S. Enteritidis from spleen and liver in an oral challenge of 10(8) S. Enteritidis without any harmful effect on BW, serum proteins, and immunoglobulin. Instead of a 21-d feeding period of beta-glucan, a 14-d treatment was enough to eliminate the S. Enteritidis in spleen and liver. In trial 3, an increase in the relative weight of bursa of Fabricius and phytohemagglutinin-P-inducing cutaneous basophil hypersensitivity was observed (P < 0.05). In trials 2, 3, and 4, the direct or indirect effect of beta-1,3-1,6-glucan on abdominal macrophages was examined. Sterilized 3% Sephadex G-50 was injected to induce abdominal (peritoneal) phagocytes in chicks fed with or without 0.1% beta-1,3-1,6-glucan. Significantly increased phagocytic and bactericidal capability to S. Enteritidis was found in abdominal macrophages either pretreated or in vitro treated with 0.1% beta-1,3-1,6-glucan. In conclusion, in addition to the physical properties to block S. Enteritidis entrance, 0.1% dietary beta-1,3-1,6-glucan may enhance the host defense to S. Enteritidis by directly upregulating the phagocytosis and bactericidal activity of abdominal macrophages in chicks.

First identified as a mediator of acquired immune tolerance of the ‘foreign’ fetus from maternal immunity, the tryptophan-catabolizing enzyme IDO (indoleamine 2,3-dioxygenase) has since been implicated in tumor escape from the host immune system. Insight into the intricate role of IDO in the classical DMBA/TPA skin carcinogenesis model suggested that inflammatory tumor environments can induce IDO production resulting in de novo tumor development. In the genetically deficient model of IDO, mice show resistance to tumor formation. This provided a basis for our current studies exploring the importance of IDO in the microenvironment of the lung. To this end, we have investigated both primary tumor formation and metastatic disease in the lungs of IDO-deficient mice using the KRAS-induced lung adenocarcinoma and the metastatic 4T1 breast cancer models. Elevation of the inflammatory cytokine IL6 was associated with tumor outgrowth in the lungs in both models but was greatly attenuated with the loss of IDO, consistent with the in vitro demonstration that IDO activity markedly potentiates IL6 production. MDSCs (myeloid derived suppressor cells) exhibited reduced T cell suppressive activity when isolated from tumor-bearing, IDO-deficient animals that could be rescued by ectopic production of IL6 in the tumor. IL6 production could likewise reverse the pulmonary metastasis resistance exhibited by IDO-deficient mice. Interestingly, while there is a clear role of the immune system in lung tumor and metastatic outgrowth, IDO-deficient mice appear to have reduced vascularization in the lung which may partly contribute to reduced tumor formation. Together, these findings genetically validate IDO as a therapeutic target in the settings of pulmonary cancer and metastasis and establish the importance of IDO as a driver of IL6 production and MDSC function. Furthermore, the correlation of IDO to angiogenesis may be a new insight into the role of this enzyme in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 295. doi:1538-7445.AM2012-295