Augmentation of Cellular Immunity and Reduction of Influenza Virus Titer in Aged Mice Fed Lactobacillus casei Strain Shirota

We investigated whether oral administration of Lactobacillus casei strain Shirota activates the cellular immune system and ameliorates influenza virus (IFV) titer in the nasal site in upper respiratory IFV infection by using aged mice. Natural killer activity of splenocytes and lung cells of aged mice fed an L. casei strain Shirota diet (L.casei strain Shirota group) was significantly (P < 0.01 and P < 0.05) increased compared to those fed a control diet (control group). The increases were 1.5- and 2.5-fold, respectively. In aged mice fed an XL.casei strain Shirota diet, potent induction of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-γ and TNF-α production increased 12- and 3.5-fold, respectively. In this model of upper respiratory IFV infection, the titer of IFV in the nasal washings of aged mice fed an L.casei strain Shirota diet was significantly (P < 0.05) lower than that in aged mice fed a control diet (10(1.6 ± 0.6) and 10(2.2 ± 0.5), respectively). These findings suggest that oral administration of L.casei strain Shirota activates not only systemic cellular immunity but also local cellular immunity and that it ameliorates IFV infection

Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the Lamina Propria and Peyer’s Patches

<div><p>Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer’s patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed <i>Lactobacillus</i> (the most abundant microbe in the small intestine), whereas CD11b^hi and CD11b^hiCD11c^hi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the <i>Lactobacillus</i> species engulfed by the SILP cell subsets, <i>L</i>. <i>murinus</i> was engulfed more frequently than <i>L</i>. <i>taiwanensis</i>, although both these <i>Lactobacillus</i> species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa.</p></div

Microscopic observations of gut microbiota engulfed by phagocytes of specific subsets.

<p>Microscopic observation of each subset was performed at a magnification of 1000 or 630 after Giemsa staining or FISH with a Cy3-conjugated Eub338 probe (total bacteria, red) and TO-PRO^®-3 (nuclei, blue), respectively. Scale bars represent 10 μm.</p

Helper T-cell differentiation-inducing properties of the phagocyte subsets.

<p>Each of the phagocyte subsets (1 × 10⁴ cells) was cocultured with OT-II splenic CD62L⁺CD44^-CD4⁺ T cells (3 × 10⁵ cells) in the presence of albumin from chicken egg white for 3.5 days and then stained intracellularly for the indicated cytokines after restimulation for 5 hours with Leukocyte Activation Cocktail with BD GolgiPlug^TM. Percentages of the indicated cytokine-positive cells among CD4⁺ T cells were determined by flow cytometry (A) and plotted with dots in bar graphs (B). Bars represent means of two independent experiments. Seven or eight C57BL/6 mice were pooled and used for each experiment.</p