Intragastric administration of Lactobacillus casei BL23 induces regulatory FoxP3+RORγt+ T cells subset in mice.

Many studies have highlighted the immunomodulatory properties of the probiotic strain Lactobacillus casei BL23. Recently, we demonstrated the ability of this strain to modulate the Th2-oriented immune response in a mouse model of cow's milk allergy based on the induction of a Th17-biased immune response. The probiotic function of L. casei has been also linked to gut-microbiota modifications which could been potentially involved in the immune regulation; however, its precise mechanism of action remains poorly understood. In this regard, recent studies suggest that gut microbiota induces a specific subset of CD4+FoxP3+ Treg cells that also express RORγt+, the specific transcription factor of Th17 cells. This new type of regulatory T cells, called type 3 Treg, displays suppressive function during intestinal inflammation, participating in inflammation control. We thus explored the ability of L. casei BL23 to specifically induce type 3 Treg cells, both in vitro and in vivo. Our results showed that intragastric administration of L. casei BL23 to mice induces local and systemic FoxP3+ RORγt+ type 3 Treg cells that could then participate in the beneficial effects of L. casei BL23 in different intestinal-related disorders.

Inactivation of the ybdD gene in Lactococcus lactis increases the amounts of exported proteins.

Random insertional mutagenesis performed on a Lactococcus lactis reporter strain led us to identify L. lactis ybdD as a protein-overproducing mutant. In different expression contexts, the ybdD mutant shows increased levels of exported proteins and therefore constitutes a new and attractive heterologous protein production host. This study also highlights the importance of unknown regulatory processes that play a role during protein secretion.

Construction and characterization of a Lactococcus lactis strain deficient in intracellular ClpP and extracellular HtrA proteases.

A Lactococcus lactis strain deficient in both its major proteases, intracellular (ClpP) and extracellular (HtrA), was constructed and characterized. This strain, hereafter called clpP-htrA, could be obtained only by conjugation between a clpP donor strain and an htrA recipient strain in the NZ9000 context, allowing heterologous gene expression under the control of the NICE (nisin-controlled expression) system. The clpP-htrA double mutant showed both higher stress tolerance (e.g. high temperature and ethanol resistance) and higher viability than single clpP or htrA mutant strains. In addition, the secretion rate of two heterologous proteins (staphylococcal nuclease Nuc and Nuc-E7) was also higher in clpP-htrA than in the wild-type strain. This strain should be a useful host for high-level production and quality of stable heterologous proteins.