Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans

Kiwamu Nakamura, Kazuya Miyagi, Yoshinobu Koguchi, Yuki Kinjo, Kaori Uezu, Takeshi Kinjo, Morikazu Akamine, Jiro Fujita, Ikuo Kawamura, Masao Mitsuyama, Yoshiyuki Adachi, Naohito Ohno, Kiyoshi Takeda, Shizuo Akira, Akiko Miyazato, Mitsuo Kaku, Kazuyoshi Kawakami

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

The present study was designed to elucidate the role of Toll-like receptor (TLR) 2 and TLR4 in the host response to Cryptococcus neoformans. Both TLR2 knockout (KO) and TLR4KO mice produced interleukin-1β (IL-1β), IL-6, IL-12p40 and tumor necrosis factor-α (TNF-α) in sera and cleared this fungal pathogen from infected lungs at a comparable level to control littermate (LM) mice. Synthesis of these cytokines was not significantly different in the lungs of these KO mice and LM mice, although IL-1β, IL-6 and IL-12p40 tended to be lower in TLR2KO, but not TLR4KO, mice than in controls. In addition, there was no significant reduction detected in the synthesis of IL-12 and TNF-α by bone marrow-derived dendritic cells from TLR2KO and TLR4KO mice upon stimulation with live yeast cells. Finally, HEK293 cells expressing either TLR2/dectin-1 or TLR4/MD2/CD14 did not respond to C. neoformans in the activation of nuclear factor kappa B (NFκB) detected by a luciferase assay. Our results suggest that TLR2 and TLR4 do not or only marginally contribute to the host and cellular response to this pathogen.

Original languageEnglish
Pages (from-to)148-154
Number of pages7
JournalFEMS Immunology and Medical Microbiology
Volume47
Issue number1
DOIs
Publication statusPublished - 2006 Jun

Keywords

  • Cryptococcus neoformans
  • Dectin-1
  • Host response
  • TLR2
  • TLR4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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