Interleukin-15 is required for maximal lipopolysaccharide-induced abortion.

The maternal immune response during pregnancy is critical for the survival of the fetus yet can be detrimental during infection and inflammation. Previously, IL-15 has been observed to mediate inflammation during LPS-induced sepsis. Therefore, we sought to determine whether IL-15 mediates the inflammatory process during LPS-induced abortion through the use of IL-15(-/-) and WT mice. Administration of 2.5 µg LPS i.p. on gd 7.5 drastically reduced fetal viability in WT mice, whereas it had a minimal effect on fetal survival in IL-15(-/-) mice. The uteroplacental sites of LPS-treated WT mice were characterized by vast structural degradation and inflammation compared with treated IL-15(-/-) and untreated controls. This suggests that IL-15 may mediate the inflammation responsible for LPS-induced resorption. As IL-15(-/-) mice are deficient in NK cells and resistant to LPS-induced abortion, these effects suggest that IL-15 may mediate abortion through their homeostatic and/or activation effects on NK cells. WT uteroplacental units exposed to LPS had an increase in the overall number and effector number of NK cells compared with their control counterparts. Furthermore, NK cell depletion before administration of LPS in WT mice partially restored fetal viability. Overall, this paper suggests that IL-15 mediates the inflammatory environment during LPS-induced fetal resorption, primarily through its effects on NK cells.

A Lactobacillus rhamnosus strain induces a heme oxygenase dependent increase in Foxp3+ regulatory T cells.

We investigated the consequences of feeding with a Lactobacillus species on the immune environment in GALT, and the role of dendritic cells and heme oxygenase-1 in mediating these responses. Feeding with a specific strain of Lactobacillus rhamnosus induced a significant increase in CD4+CD25+Foxp3+ functional regulatory T cells in GALT. This increase was greatest in the mesenteric lymph nodes and associated with a marked decrease in TNF and IFNγ production. Dendritic cell regulatory function and HO-1 expression was also increased. The increase in Foxp3+ T cells could be prevented by treatment with a heme oxygenase inhibitor. However, neither inhibition of heme oxygenase nor blockade of IL-10 and TGFß prevented the inhibition of inflammatory cytokine production. In conclusion Lactobacillus feeding induced a tolerogenic environment in GALT. HO-1 was critical to the enhancement of Foxp3+ regulatory T cells while additional, as yet unknown, pathways were involved in the down-regulation of inflammatory cytokine production by T cells.