Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s) of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031).Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56), and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction.These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.The intestinal immune system must co-exist with resident commensal microorganisms while maintaining the ability to defend against potential microbial challenge. This immune tolerance is a highly regulated process comprised of a myriad of biological checkpoints necessary to maintain homeostasis between the host and the gut microbiota [1]. In instances of inflammatory bowel disease (IBD), this tolerance between immune cells and intestinal bacteria is disrupted; however, causes of this tolerance breakdown have not yet been determined [2,3]. Although the etiology of IBD is still unknown, exaggerated inflammation induced by activated innate immune cells via their interaction with the microbiota and their gene products, as well as infiltrating CD4+ IFNγ+ T cells, likely play key roles in uncontrolled inflammation and tissue dest