Outer Membrane Vesicles Attenuate <i>Klebsiella pneumoniae</i> Infection Injury by Affecting Macrophage Polarisation and Helper T Cell Differentiation.

Abstract

<i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) is an opportunistic bacteria that can result in severe liver abscesses, pulmonary damage, and potentially fatal outcomes. Research has demonstrated that the outer membrane vesicles (OMVs) released by it can provide significant protection to infected animals and may serve as a promising candidate antigen for the development of a novel vaccine. Nevertheless, the specific mechanisms through which OMVs mitigate the detrimental effects of <i>K. pneumoniae</i> infection by promoting the polarization pathways of macrophages and T helper cells (Th cells) remain poorly understood. In this study, we first confirmed that <i>Klebsiella pneumoniae</i> outer membrane vesicles (<i>K. pneumoniae</i>_OMVs) were protective in <i>K. pneumoniae</i>-infected mice, and then we investigated the protective mechanisms by transcriptome data analysis. Then, we constructed a model of in vitro macrophage polarization, an in vivo model for Th differentiation, and a <i>K. pneumoniae</i> infection model in <i>K. pneumoniae</i>_OMVs-immunized mice. qRT-PCR, IHC, Western blotting, and ELISA were used to confirm the polarization indicators. The results showed that <i>K. pneumoniae</i>_OMVs were able to provide specific protection for mice with a maximum protection rate of 80%. In addition, the results of a transcriptome analysis suggested that the protective mechanism might be related to Th cells and macrophage polarization. Mice immunized with <i>K. pneumoniae</i>_OMVs were able to achieve rapid bacterial clearance after <i>K. pneumoniae</i> infection through an M1/Th1 immune response. Subsequently, tissue repair was accomplished through Th2/M2 immune response in the late stage of <i>K. pneumoniae</i> infection to avoid causing inflammatory damage. This study offers a theoretical foundation for the <i>K. pneumoniae</i>_OMVs vaccine's actual application.