Differential roles of toll-like receptors 2 and 4 in in vitro responses of macrophages to Legionella pneumophila

Morikazu Akamine, Futoshi Higa, Noriko Arakaki, Kazuyoshi Kawakami, Kiyoshi Takeda, Shizuo Akira, Atsushi Saito

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

The role of Toll-like receptors (TLRs) in innate immunity to Legionella pneumophila, a gram-negative facultative intracellular bacterium, was studied by using bone marrow-derived macrophages and dendritic cells from TLR2-deficient (TLR2-/-), TLR4-/-, and wild-type (WT) littermate (C57BL/6 × 129Sv) mice. Intracellular growth of L. pneumophila was enhanced within TLR2-/- macrophages compared to WT and TLR4-/- macrophages. There was no difference in the bacterial growth within dendritic cells from WT and TLR-deficient mice. Production of interleulkin-12p40 (IL-12p40) and IL-10 after infection with L. pneumophila was attenuated in TLR2-/- macrophages compared to WT and TLR4-/- macrophages. Induction of IL-12p40, IL-10, and tumor necrosis factor alpha secretion from macrophages by the L. pneumophila dotO mutant, which cannot multiply within macrophages, and heat-killed bacteria, was similar to that caused by a viable virulent strain. There was no difference between the WT and its mutants in susceptibility to the cytopathic effect of bacteria. An L. pneumophila sonicated lysate induced IL-12p40 production by macrophages, but that of TLR2-/- macrophages was significantly lower than those of WT and TLR4-/- macrophages. Treatment of L. pneumophila sonicated lysate with proteinase K and heating did not abolish TLR2-dependent IL-12p40 production. Our results show that TLR2, but not TLR4, is involved in murine innate immunity against L. pneumophila, although other TLRs may also contribute to innate immunity against this organism.

Original languageEnglish
Pages (from-to)352-361
Number of pages10
JournalInfection and immunity
Volume73
Issue number1
DOIs
Publication statusPublished - 2005 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Differential roles of toll-like receptors 2 and 4 in in vitro responses of macrophages to Legionella pneumophila'. Together they form a unique fingerprint.

Cite this