Identifying Friend or Foe - Mreg?

How do the immune cells within the gut distinguish between potentially dangerous pathogens and harmless or beneficial commensal organisms? [Hint: It’s not through PAMPs (pathogen-associated molecular patterns.)]

These investigators identified in mice a novel population of macrophages within the lamina propria, the layer of mucosa beneath the epithelium on the lumenal side of the intestine wall. These macrophages secrete IL-10 and other anti-inflammatory cytokines but no pro-inflammatory cytokines (even when stimulated through their Toll-like receptors by PAMPs). They also stimulate the development of regulatory T cells (Tregs) more potently than splenic macrophages (figure, CD4+ FoxP3+ Treg) and suppress the secretion of IL-17 by DC within the lamina propria. The authors suggest that a “dynamic interaction between these subsets may influence the balance between immune activation and tolerance”. They need to abbreviate the idea... how about 'Mregs'?

Denning et al. "Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses". Nat Immunol. 2007 Oct;8(10):1086-94.

Targeting the Plant Inside

Toxoplasm gondii are intracellular parasites that cause toxoplasmosis, the “third leading cause of death attributed to foodborne illness in the United States. More that 60 million [Americans] carry the Toxoplasma parasite, but very few have symptoms because the immune system usually keeps the parasite from causing illness” (CDC). T.gondii contain organelles or plastids called “apicoplasts” that were probably acquired in evolution along with an algal endosymbiont.

Apicoplasts contain unique proteins that may be effectively targeted by therapeutic agents. These researchers previously demonstrated a calcium control of protein secretion and identified conserved Ca-responsive proteins. Here they show that calcium-dependent development in T. gondii is controlled by a plant hormone produced by the apicoplast, abscisic acid (ABA, named for its role in abscission, the shedding of plant leaves, fruit, etc.). They found that fluridone, an herbicide that specifically inhibits an enzyme on the synthetic pathway producing ABA, blocked T gondii maturation. Finally, they demonstrated that the herbicide also worked as a therapeutic, protecting mice from a lethal dose of T gondii (shown, from Figure 4). Another infamous apicoplast-containing parasite is Plasmodium falciparum, which causes severe malaria, suggesting an exciting new approach to treating this scourge.

Nagamune et al. "Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii" Nature. 2008 Jan 10;451(7175):207-10.