Lactocepin Secreted By Lactobacillus Exerts Anti-Inflammatory Effects By Selectively Degrading Proinflammatory Chemokines

Abstract

The intestinal microbiota has been linked to inflammatory bowel diseases (IBD), and oral treatment with specific bacteria can ameliorate IBD. One bacterial mixture, VSL#3, containing Lactobacillus, Bifidobacterium, and Streptococcus, was clinically shown to reduce inflammation in IBD patients and normalize intestinal levels of IP-10, a lymphocyte-recruiting chemokine, in a murine colitis model. We identified Lactobacillus paracasei prtP-encoded lactocepin as a protease that selectively degrades secreted, cell-associated, and tissue-distributed IP-10, resulting in significantly reduced lymphocyte recruitment after intraperitoneal injection in an ileitis model. A human Lactobacillus casei isolate was also found to encode lactocepin and degrade IP-10. L. casei feeding studies in a murine colitis model (T cell transferred Rag2(-/-) mice) revealed that a prtP-disruption mutant was significantly less potent in reducing IP-10 levels, T cell infiltration and inflammation in cecal tissue compared to the isogenic wild-type strain. Thus, lactocepin-based therapies may be effective treatments for chemokine-mediated diseases like IBD.

Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model

“…Inflammatory scores of mice exposed to DSS were highly divergent between cages of mice with an acquired biome compared with those that were gavaged (Figures 6b and d). Interestingly, Lactobacillus, a taxa that is generally considered to have anti-inflammatory properties (Servin, 2004;Santos Rocha et al, 2012;von Schillde et al, 2012), was found to be significantly associated with time, treatment  time and treatment under the mixed linear model analysis of the gavage vs acquired data set (Figures 6a and c; Supplementary Table S3). With our small sample size, we cannot meaningfully speculate on whether these associations are robust and would be reproducible in future cohorts.…”

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

“…the Lactobacillus rhamnosus GG strain) may possess beneficial effects in IBD [151] and recent evidences indicate that Lactobacillus salivarius Ls33 is able to inhibit experimentally induced colitis in a NOD2-dependent manner [152]. Furthermore, von Schillde et al identified a Lactobacillus paracasei prtP-encoded protease named lactocepin, which degrades the pro-inflammatory chemokine IP-10 (interferon gamma-induced protein 10) and consequently alleviates colonic inflammation [153]. Thus, a reduced amount of Lactobacillus may contribute to the pathogenesis of IBD.…”

RecombinantLactobacillus plantaruminduces immune responses to cancer testis antigen NY-ESO-1 and maturation of dendritic cells

“…www.tandfonline.comprovide an important regulatory mechanism and may explain their anti-inflammatory and protective effects 22,28 Most studies in the literature have focused on mucosal vaccination against infections. 1 With respect to cancer immunotherapy, recently Kawana and colleagues demonstrated that oral vaccination with L. casei expressing modified E7 protein can induce clinical response in patients with cervical intraepithelial neoplasia.…”

“…20,21 In contrast to the currently used vectors, LAB are generally regarded as safe microorganisms, and some of them are able to stimulate the immune system of the host as adjuvants due to their probiotic and anti-inflammatory properties. 1,22 Except for cervical cancer, little is known about the use of LAB in cancer vaccines. We previously reported that the 37 kDa immunogenic oncofetal antigen (OFA) expressed on the cell surface of L. plantarum can induce antibody response.…”