Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice

Elife. 2021 Sep 20;10:e69951. doi: 10.7554/eLife.69951.

Abstract

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

Keywords: Acinetobacter baumannii; Trained immunity; acinetobacter baumannii; alveolar macrophage; immunology; infectious disease; inflammation; klebsiella pneumoniae; microbiology; multidrug-resistant bacteria; pseudomonas aeruginosa; rapid effect; trained immunity; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / immunology
  • Acinetobacter Infections / microbiology
  • Acinetobacter Infections / prevention & control*
  • Acinetobacter baumannii / immunology*
  • Administration, Intranasal
  • Adoptive Transfer
  • Animals
  • Bacterial Vaccines / administration & dosage*
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Homeodomain Proteins / genetics
  • Immunity, Innate / drug effects
  • Klebsiella Infections / immunology
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / prevention & control*
  • Klebsiella pneumoniae / immunology*
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / microbiology
  • Macrophages, Alveolar / transplantation
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / prevention & control*
  • Pseudomonas Infections / immunology
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / prevention & control*
  • Pseudomonas aeruginosa / immunology*
  • Time Factors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination
  • Vaccines, Inactivated / administration & dosage

Substances

  • Bacterial Vaccines
  • Homeodomain Proteins
  • Tlr4 protein, mouse
  • Tnf protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Vaccines, Inactivated
  • RAG-1 protein

Associated data

  • GEO/GSE141729

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.