Sweet! Helicobacter Sugar Calms Intestinal Macrophages Calum C. Bain, Marika C. Kullberg  Cell Host & Microbe  Volume 22, Issue 6, Pages 719-721 (December 2017) DOI: 10.1016/j.chom.2017.11.014 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Polysaccharide(s) from the Bacterium Helicobacter hepaticus Promote(s) Mutualism with the Host by Inducing Cecal Macrophage IL-10 Production Helicobacter hepaticus (Hh) produces a polysaccharide, or polysaccharides, that bind(s) to TLR2 on cecal macrophages to stimulate the production of the immunoregulatory cytokine IL-10, a factor that is key to establishing mutualism between Hh and its host (Kullberg et al., 1998, 2006). This pathway relies on the TLR adaptor MyD88 and downstream signaling molecules Erk1/2 and Msk1/2, which leads to CREB translocation to the nucleus and induction of IL-10 transcription. Macrophage-derived IL-10 plays important, albeit not indispensable, roles in maintaining intestinal homeostasis, e.g., through the maintenance of regulatory T cells (Hadis et al., 2011). Furthermore, IL-10 may act in an autocrine manner on macrophages to negatively regulate TLR responsiveness (Mowat et al., 2017). Mice lacking the IL-10 receptor (IL-10R) specifically in macrophages develop severe enterocolitis (Zigmond et al., 2014), demonstrating the importance of IL-10R signaling in this innate immune cell population for the maintenance of a healthy intestine. Solid arrows represent work described in the paper by Danne et al. (2017), while dashed black arrows represent two potential mechanisms by which IL-10 may promote mutualism between microbe and host based on published literature (Hadis et al., 2011; Mowat et al., 2017). Dashed gray arrows represent unknown mechanisms and interactions, e.g., how Hh polysaccharide reaches the lamina propria and whether the active Hh component acts on other TLR2+ cells in the cecum and/or colon. Hh, H. hepaticus; TLR, Toll-like receptor; Treg, regulatory T cell. Cell Host & Microbe 2017 22, 719-721DOI: (10.1016/j.chom.2017.11.014) Copyright © 2017 Elsevier Inc. Terms and Conditions