Enhanced Antiinflammatory Capacity of a Lactobacillus plantarum Mutant Synthesizing Modified Teichoic Acids

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-07, Vol.102 (29), p.10321-10326
• Main Authors: Grangette, Corinne, Nutten, Sophie, Palumbo, Emmanuelle, Morath, Siegfried, Hermann, Corinna, Dewulf, Joelle, Pot, Bruno, Hartung, Thomas, Hols, Pascal, Mercenier, Annick, Klaenhammer, Todd R.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Anti-Inflammatory Agents - therapeutic use; Antiinflammatories; Bacteria; Biological Sciences; Bone marrow cells; Cloning, Molecular; Colitis; Colitis - drug therapy; Colitis - metabolism; Cytokines; Cytokines - metabolism; DNA Primers; Genetic Vectors - genetics; Humans; Immune system; Immunologic Factors - therapeutic use; Immunology; Lactobacillus plantarum - genetics; Lactobacillus plantarum - immunology; Lactobacillus plantarum - metabolism; Leukocytes, Mononuclear - metabolism; Lipopolysaccharides - biosynthesis; Lipopolysaccharides - therapeutic use; Membrane Transport Proteins - genetics; Mice; Mice, Inbred BALB C; Microbiology; Monocytes; Mutation; Mutation - genetics; Pathogens; Saliva - microbiology; Secretion; Teichoic acids; Teichoic Acids - biosynthesis; Teichoic Acids - therapeutic use
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0504084102

Teichoic acids (TAs), and especially lipoteichoic acids (LTAs), are one of the main immunostimulatory components of pathogenic Gram-positive bacteria. Their contribution to the immunomodulatory properties of commensal bacteria and especially of lactic acid bacteria has not yet been investigated in detail. To evaluate the role of TAs in the interaction between lactic acid bacteria and the immune system, we analyzed the antiinflammatory properties of a mutant of Lactobacillus plantarum NCIMB8826 affected in the TA biosynthesis pathway both in vitro (mononuclear cells stimulation) and in vivo (murine model of colitis). This Dlt-mutant was found to incorporate much less D-Ala in its TAs than the WT strain. This defect significantly impacted the immunomodulation reactions induced by the bacterium, as shown by a dramatically reduced secretion of proinflammatory cytokines by peripheral blood mononuclear cells and monocytes stimulated by the Dlt-mutant as compared with the parental strain. Concomitantly, a significant increase in IL-10 production was stimulated by the Dlt-mutant in comparison with the WT strain. Moreover, the proinflammatory capacity of L. plantarum-purified LTA was found to be Toll-like receptor 2-dependent. Consistent with the in vitro results, the Dlt-mutant was significantly more protective in a murine colitis model than its WT counterpart. The results indicated that composition of LTA within the whole-cell context of L. plantarum can modulate proinflammatory or antiinflammatory immune responses.