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

Abstract

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. ABSTRACT 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 Lactobacillus plantarum CIRM653 on the inflammatory response induced by the pathogen Klebsiella pneumoniae. Oral administration of L. plantarum CIRM653 to mice subsequently infected by K. pneumoniae 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. In vitro coincubation of L. plantarum CIRM653 and K. pneumoniae 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 K. pneumoniae-infected cells. Neither K. pneumoniae nor L. plantarum CIRM653 had any effect on cytokine production by intestinal epithelial cells in vitro, but the induction of the NF-κB pathway and IL-8 and IL-6 production by K. pneumoniae in airway epithelial cells was significantly reduced when the pathogen was coincubated with L. plantarum CIRM653. The remote IL-10-mediated modulation of the K. pneumoniae inflammatory response by L. plantarum CIRM653 supports the concept of immunomodulation by beneficial bacteria through the gut-lung axis.