Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae.

Some respiratory infections have been associated with dysbiosis of the intestinal microbiota. The underlying mechanism is incompletely understood, but cross talk between the intestinal microbiota and local immune cells could influence the immune response at distal mucosal sites. This has led to the concept of enhancing respiratory defenses by modulating the intestinal microbiota with exogenous supplementation of beneficial strains. In this study, we examined the effect of CIRM653 on the inflammatory response induced by the pathogen Oral administration of CIRM653 to mice subsequently infected by via the nasal route (i) reduced the pulmonary inflammation response, with decreased numbers of lung innate immune cells (macrophages and neutrophils) and cytokines (mouse keratinocyte-derived chemokine [KC], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNF-α]) in the bronchoalveolar fluid, and (ii) induced an immunosuppressive Treg response in lungs. coincubation of CIRM653 and with human dendritic cells and peripheral blood mononuclear cells resulted in decreased Th1 (IL-12p70 and interferon gamma [IFN-γ]) and Th17 (IL-23 and IL-17) and increased Treg (IL-10) cytokine levels compared to those observed for -infected cells. Neither nor CIRM653 had any effect on cytokine production by intestinal epithelial cells , but the induction of the NF-κB pathway and IL-8 and IL-6 production by in airway epithelial cells was significantly reduced when the pathogen was coincubated with CIRM653. The remote IL-10-mediated modulation of the inflammatory response by CIRM653 supports the concept of immunomodulation by beneficial bacteria through the gut-lung axis.