Leptospira interrogans is recognized through DC-SIGN and induces maturation and cytokine production by human

Narintorn Gaudart1, Pattama Ekpo, Kovit Pattanapanyasat

  • 1Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Insights

Leptospira interrogans, a cause of leptospirosis, binds to dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and triggers immune cell maturation. This interaction influences cytokine production, offering insights into the immune response to this zoonotic disease.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Leptospirosis, a global zoonotic disease caused by Leptospira species, presents significant public health and livestock challenges.
  • The pathogenesis, immune response, and cellular receptors involved in Leptospira infections remain incompletely understood.
  • Dendritic cells (DCs) play a crucial role in initiating adaptive immune responses to pathogens.

Purpose of the Study:

  • To investigate the interaction between Leptospira interrogans serovars and dendritic cells (DCs).
  • To elucidate the role of DC-SIGN in the attachment of Leptospira to DCs.
  • To analyze the impact of L. interrogans infection on DC maturation and cytokine production.

Main Methods:

  • Carbohydrate analysis of L. interrogans strains using lectins.
  • Investigation of L. interrogans attachment to DCs.
  • Assessment of DC maturation markers post-interaction.
  • Quantification of cytokine production (IL-10, IL-12p70, TNF-alpha) by DCs.

Main Results:

  • All investigated L. interrogans strains possessed high mannose components, suggesting a common backbone.
  • DC-SIGN was identified as a key receptor involved in the attachment of L. interrogans to DCs.
  • L. interrogans interaction induced DC maturation, with varying effects on cytokine profiles.
  • Specific strains (Pyrogenes 2317 and Autumnalis BL-6) induced IL-12p70 and TNF-alpha, but minimal IL-10.

Conclusions:

  • Leptospira interrogans utilizes DC-SIGN for binding to dendritic cells.
  • L. interrogans binding induces DC maturation and modulates cytokine production.
  • These findings provide novel insights into the cellular immune mechanisms underlying leptospirosis.