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. 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.

The Gut Microbiota and Respiratory Diseases: New Evidence

“…Oral administration of probiotics contributes to regulating respiratory immune responses through numerous signaling pathways. For example, Bifidobacterium bifidum can stimulate the Th1/Th2 balance and upregulate IFN-γ, IL-4, and IL-12 secretion in the spleen [139]; Escherichia coli can reduce respiratory inflammatory cell recruitment as well as Th2 and Th17 responses [140]; Enterococcus faecalis suppresses Th17 cell development in the lung, spleen, and gut [141]; and Lactobacillus plantarum can reduce the numbers of lung innate immune cells (macrophages and neutrophils) and levels of cytokines (IL-6 and TNF-α) in the BALF and induce an immunosuppressive Treg response in the lungs [142]. Despite these effects, the precise mechanisms underlying probiotic effects on the lung and many aspects of the probiotic regulation of immune responses remain largely unknown.…”

Lacticaseibacillus casei AMBR2 modulates the epithelial barrier function and immune response in a donor-derived nasal microbiota manner

“…We observed an increase in IL-10 release in triple co-culture systems, albeit in 100-fold lower concentrations than observed by Rocha-Ramirez et al 72 , possibly due to the lack of direct contact between macrophages and bacterial cell wall compounds, and their use of primary human monocyte derived macrophages instead of the THP-1 cell line. In mice, remote induction of IL-10 by Lactobacillus plantarum, reclassified as Lactiplantibacillus plantarum 42 in the gut could reduce the induction of IL-8 after nasal infection with Klebsiella pneumoniae 74 , a mechanism which might possibly explain the reduced IL-8 release in our triple co-culture model system. This underlines the importance of incorporating immune cells as well as epithelial cells to study host-microbe interactions in the URT.…”

Bacteriophages isolated from dairy farm mitigated Klebsiella pneumoniae-induced inflammation in bovine mammary epithelial cells cultured in vitro

“…K. pneumoniae can infect a variety of cells and tissues, inducing inflammatory responses and cell damage [ 23 – 25 ]. In addition, it also infects bMECs in development of mastitis in dairy cows [ 26 ].…”