Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells.
Dendritic cells (DC) play a pivotal immunoregulatory role in the Th1, Th2, and Th3 cell balance and are present throughout the gastrointestinal tract. Thus, DC may be targets for modulation by gut microbes, including ingested probiotics. In the present study, we tested the hypothesis that species of Lactobacillus, important members of the gut flora, differentially activate DC. Bone marrow-derived murine DC were exposed to various lethally irradiated Lactobacillus spp. and resultant culture supernatants were analyzed for IL-6, IL-10, IL-12, and TNF-alpha. Substantial differences were found among strains in the capacity to induce IL-12 and TNF-alpha production in the DC. Similar but less pronounced differences were observed among lactobacilli in the induction of IL-6 and IL-10. Although all strains up-regulated surface MHC class II and B7-2 (CD86), which is indicative of DC maturation, those lactobacilli with greatest capacity to induce IL-12 were most effective. Remarkably, Lactobacillus reuteri DSM12246, a poor IL-12 inducer, inhibited IL-12, IL-6, and TNF-alpha induction by the otherwise strong cytokine inducer L. casei CHCC3139, while IL-10 production remained unaltered. In analogous fashion, L. reuteri reduced L. casei-induced up-regulation of B7-2. These results suggest that different species of Lactobacillus exert very different DC activation patterns and, furthermore, at least one species may be capable of inhibiting activities of other species in the genus. Thus, the potential exists for Th1/Th2/Th3-driving capacities of the gut DC to be modulated according to composition of gut microflora, including ingested probiotics.
Christensen
Hanne R
HR
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Frøkiaer
Hanne
H
Pestka
James J
JJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D018928:Immunity, Mucosal; D007778:Lactobacillus / Q000502:physiology*; D007780:Lacticaseibacillus casei / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins