TY - JOUR
T1 - Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid
AU - Zadeh, Mojgan
AU - Khan, Mohammad W.
AU - Goh, Yong Jun
AU - Selle, Kurt
AU - Owen, Jennifer L.
AU - Klaenhammer, Todd
AU - Mohamadzadeh, Mansour
N1 - Funding Information:
This work was supported in part by the by NIH Grant 1R01AI098833-01, Danisco USA, and the North Carolina Dairy Foundation. We also thank Dr. Praveen Bere, Dr. Mary Brown, and Robert Roman for their generous support and excellent technical assistant and discussion of this work.
PY - 2012
Y1 - 2012
N2 - Background: The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. Methods. 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). Results: 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. Conclusions: 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.
AB - Background: The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. Methods. 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). Results: 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. Conclusions: 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.
KW - Dendritic cells
KW - Dextran sulfate sodium
KW - Inflammatory bowel disease
KW - Lipoteichoic acid
KW - Toll-like receptor 2
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U2 - 10.1186/1476-9255-9-7
DO - 10.1186/1476-9255-9-7
M3 - Article
C2 - 22423982
AN - SCOPUS:84863418169
SN - 1476-9255
VL - 9
JO - Journal of Inflammation
JF - Journal of Inflammation
M1 - 7
ER -