Yersinia pseudotuberculosis Exploits CD209 Receptors for Promoting Host Dissemination and Infection

Area of Science:

• Microbiology
• Immunology
• Infectious Diseases

Background:

• Yersinia pseudotuberculosis is a Gram-negative enteropathogen causing gastrointestinal infections and disseminating to organs like the spleen and liver.
• The precise molecular mechanisms governing Y. pseudotuberculosis dissemination from the gut remain incompletely understood.
• Peyer's patches are hypothesized entry points for many Gram-negative pathogens initiating systemic spread.

Purpose of the Study:

• To elucidate the molecular interactions enabling Y. pseudotuberculosis dissemination.
• To investigate the role of CD209 receptors in Y. pseudotuberculosis infection and spread.
• To identify potential targets for blocking bacterial dissemination.

Main Methods:

• Investigated Y. pseudotuberculosis interaction with CD209 receptors on human dendritic cells and murine macrophages.
• Utilized wild-type and Peyer's patch-deficient mice to assess bacterial dissemination.
• Examined the effect of blocking Y. pseudotuberculosis-CD209 interactions using O-antigen and oligosaccharides on infectivity.

Main Results:

• Y. pseudotuberculosis lipopolysaccharide (LPS) core interacts with CD209 receptors, mediating invasion of dendritic cells and macrophages.
• CD209-mediated interactions facilitate bacterial dissemination to mesenteric lymph nodes, spleen, and liver in mice.
• Blocking these interactions with O-antigen or oligosaccharides significantly reduced bacterial infectivity.

Conclusions:

• Y. pseudotuberculosis hijacks the CD209-mediated pathway, involving antigen-presenting cells, for dissemination after penetrating the intestinal barrier.
• This interaction is crucial for the pathogen's spread to target organs such as mesenteric lymph nodes, spleen, and liver.
• Targeting the Y. pseudotuberculosis-CD209 interaction presents a potential strategy to combat infections caused by this enteropathogen.