Some respiratory infections have been associated with dysbiosis of the intestinal microbiota. The underlying mechanism is incompletely understood but crosstalk between intestinal microbiota and local immune cells could influence the immune response at distal mucosal sites. This has led to the concept of enhancing respiratory defences 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 (KC, IL-6 and TNF-alpha) in the bronchoalveolar fluid and ii) induced an immunosuppressive Treg response in lungs. In vitro co-incubation of L. plantarum CIRM653 and K. pneumoniae with human dendritic cells and peripheral blood mononuclear cells resulted in decreased Th1 (IL-12p70; IFN-gamma) and Th17 (IL-23, IL-17) and increased Treg (IL-10) cytokine levels compared to those observed with 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 NF-kappaB pathway and IL-8 and IL-6 production by K. pneumoniae in airway epithelial cells was significantly reduced when the pathogen was co-incubated with L. plantarum CIRM653 The remote IL-10-mediated modulation of K pneumoniae inflammatory response by L. plantarum CIRM653 supports the concept of immunomodulation by beneficial bacteria through the gut-lung axis.