A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana

Toni Aebischer, Clare L. Bennett, Mattia Pelizzola, Caterina Vizzardelli, Norman Pavelka, Matteo Urbano, Monica Capozzoli, Alessandra Luchini, Thomas Ilg, Francesca Granucci, C. Clare Blackburn, Paola Ricciardi-Castagnoli

Research output: Contribution to journalArticlepeer-review

Abstract

Recognition of pathogen-associated molecular patterns (PAMP) influences the response of dendritic cells (DC) and therefore development of innate and adaptive immunity. Different forms of Leishmania mexicana have distinct effects on DC, with promastigotes and amastigotes being activating and apparently neutral, respectively. We investigated whether stage-specific differences in surface composition might account for these distinct effects. Amastigotes and promastigotes lacking the lpg1 gene needed for lipophosphoglycan (LPG) biosynthesis could not activate DC in vitro. Genome-wide transcriptional profiling of DC infected with wild-type or mutant promastigotes or wild-type amastigotes revealed that wild-type promastigotes induce an inflammatory signature that is lacking in DC exposed to the other parasite forms. The proinflammatory response pattern was partly recovered by reconstitution of lpg1 expression in lpg1-/- parasites, and exposure to purified LPG increased the expression of MHC class II and CD86 on DC. Infection with wild-type but not lpg1-/- promastigotes increased the number of activated DC in draining lymph nodes, and this was correlated with lower early parasite burdens in wild-type-infected animals. These in vivo and in vitro results suggest an LPG-dependent activation of DC that contributes to host defense and agree with the notion that the parasites evolved under immune pressure to down-regulate PAMP expression in mammalian hosts.

Original languageEnglish
Pages (from-to)476-486
Number of pages11
JournalEuropean Journal of Immunology
Volume35
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Cellular activation
  • Dendritic cells
  • Inflammation
  • Leishmania
  • Parasitic-protozoan

ASJC Scopus subject areas

  • Immunology

Fingerprint

Dive into the research topics of 'A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana'. Together they form a unique fingerprint.

Cite this