Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

Mojgan Zadeh, Mohammad W. Khan, Yong Jun Goh, Kurt Selle, Jennifer L. Owen, Todd Klaenhammer, Mansour Mohamadzadeh

Producción científica: Articlerevisión exhaustiva

26 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Número de artículo7
PublicaciónJournal of Inflammation
Volumen9
DOI
EstadoPublished - 2012
Publicado de forma externa

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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