title: S-layer protein mediates the stimulatory effect of Lactobacillus helveticus MIMLh5 on innate immunity.
abstract: The ability to positively affect host health through the modulation of the immune response is a feature of increasing importance in measuring the probiotic potential of a bacterial strain. However, the identities of the bacterial cell components involved in cross talk with immune cells remain elusive. In this study, we characterized the dairy strain Lactobacillus helveticus MIMLh5 and its surface-layer protein (SlpA) using in vitro and ex vivo analyses. We found that MIMLh5 and SlpA exert anti-inflammatory effects by reducing the activation of NF-κB on the intestinal epithelial Caco-2 cell line. On the contrary, MIMLh5 and SlpA act as stimulators of the innate immune system by triggering the expression of proinflammatory factors tumor necrosis factor alpha and COX-2 in the human macrophage cell line U937 via recognition through Toll-like receptor 2. In the same experiments, SlpA protein did not affect the expression of the anti-inflammatory cytokine interleukin-10. A similar response was observed following stimulation of macrophages isolated from mouse bone marrow or the peritoneal cavity. These results suggest that SlpA plays a major role in mediating bacterial immune-stimulating activity, which could help to induce the host's defenses against and responses toward infections. This study supports the concept that the viability of bacterial cells is not always essential to exert immunomodulatory effects, thus permitting the development of safer therapies for the treatment of specific diseases according to a paraprobiotic intervention.
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Taverniti
authors.forename: Milda
authors.initials: M
authors.lastname: Stuknyte
authors.forename: Mario
authors.initials: M
authors.lastname: Minuzzo
authors.forename: Stefania
authors.initials: S
authors.lastname: Arioli
authors.forename: Ivano
authors.initials: I
authors.lastname: De Noni
authors.forename: Christian
authors.initials: C
authors.lastname: Scabiosi
authors.forename: Zuzet Martinez
authors.initials: ZM
authors.lastname: Cordova
authors.forename: Ilkka
authors.initials: I
authors.lastname: Junttila
authors.forename: Sanna
authors.initials: S
authors.lastname: Hämäläinen
authors.forename: Hannu
authors.initials: H
authors.lastname: Turpeinen
authors.forename: Diego
authors.initials: D
authors.lastname: Mora
authors.forename: Matti
authors.initials: M
authors.lastname: Karp
authors.forename: Marko
authors.initials: M
authors.lastname: Pesu
authors.forename: Simone
authors.initials: S
authors.lastname: Guglielmetti
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000494:pharmacology*; D052198:Lactobacillus helveticus / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D019936:Probiotics / Q000494:pharmacology*; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007155:Immunologic Factors; C070683:surface layer protein A, Bacteria