Role of interleukin-1β in activating the CD11chigh CD45RB- dendritic cell subset and priming Leishmania amazonensis- specific CD4+ T cells in vitro and in vivo

Lijun Xin, Yongguo Li, Lynn Soong

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Cutaneous leishmaniasis associated with Leishmania amazonensis infection is characterized by uncontrolled parasite replication and profound immunosuppression; however, the underlying mechanisms remain largely unclear. One possibility is that the L. amazonensis parasite modulates antigen-presenting cells, favoring the generation of pathogenic Th cells that are capable of recruiting leukocytes but insufficient to fully activate their microbicidal activities. To test this possibility, we infected bone marrow-derived dendritic cells (DCs) of C57BL/6 mice with L. amazonensis or Leishmania major promastigotes and assessed the activation of DC subsets and their capacity in priming CD4+ T cells in vitro. In comparison to L. major controls, L. amazonensis-infected DCs secreted lower levels of interleukin-1α (IL-1α) and IL-1β, were less potent in activating the IL-12p40-producing CD11chigh CD45RB- CD83+ CD40+ DC subset, and preferentially activated CD4+ T cells with a IFN-γlow IL-10high IL-17high phenotype. Although the addition of IL-1β at the time of infection markedly enhanced DC activation and T-cell priming, it did not skew the cytokine profile of DCs and pathogenic Th cells, as local injection of IL-1β following L. amazonensis infection accelerated Th cell activation and disease progression. This study suggests that intrinsic defects at the level of DC activation are responsible for the susceptible phenotype in L. amazonensis-infected hosts and that this parasite may have evolved unique mechanisms to interfere with innate and adaptive immunity.

Original languageEnglish (US)
Pages (from-to)5018-5026
Number of pages9
JournalInfection and immunity
Volume75
Issue number10
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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