The unique Legionella longbeachae capsule favors intracellular replication and immune evasion

PLoS Pathog. 2024 Sep 11;20(9):e1012534. doi: 10.1371/journal.ppat.1012534. eCollection 2024 Sep.

Abstract

Legionella longbeachae and Legionella pneumophila are the most common causative agents of Legionnaires' disease. While the clinical manifestations caused by both species are similar, species-specific differences exist in environmental niches, disease epidemiology, and genomic content. One such difference is the presence of a genomic locus predicted to encode a capsule. Here, we show that L. longbeachae indeed expresses a capsule in post-exponential growth phase as evidenced by electron microscopy analyses, and that capsule expression is abrogated when deleting a capsule transporter gene. Capsule purification and its analysis via HLPC revealed the presence of a highly anionic polysaccharide that is absent in the capsule mutant. The capsule is important for replication and virulence in vivo in a mouse model of infection and in the natural host Acanthamoeba castellanii. It has anti-phagocytic function when encountering innate immune cells such as human macrophages and it is involved in the low cytokine responses in mice and in human monocyte derived macrophages, thus dampening the innate immune response. Thus, the here characterized L. longbeachae capsule is a novel virulence factor, unique among the known Legionella species, which may aid L. longbeachae to survive in its specific niches and which partly confers L. longbeachae its unique infection characteristics.

MeSH terms

  • Acanthamoeba castellanii / microbiology
  • Animals
  • Bacterial Capsules* / immunology
  • Bacterial Capsules* / metabolism
  • Humans
  • Immune Evasion*
  • Legionella longbeachae* / immunology
  • Legionnaires' Disease / immunology
  • Legionnaires' Disease / microbiology
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Virulence
  • Virulence Factors / metabolism

Substances

  • Virulence Factors

Grants and funding

This work is supported by the French Government (grants ANR-10-LABX-62-IBEID to C.B.) and the “Fondation pour la Recherche Médicale” (grant EQU201903007847 to C.B.). S.S. is a scholar in the Pasteur-Paris University (PPU) International Ph.D. program and received stipends from the Institut Pasteur and the “Fondation pour la Recherche Médicale” (FDT202204015116). We gratefully acknowledge the kind financial support of the Institut Pasteur (Paris) and the Région Ile-de-France (program DIM1Health to UTechs PBI). Work in the D.S.Z. laboratory is financed by The São Paulo Research Foundation (FAPESP grant 2019/11342-6). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.