Toll-like receptor 4 is not required for the full maturation of dendritic cells or for the degradation of Gram-negative bacteria

Maria Rescigno, Matteo Urbano, Monica Rimoldi, Barbara Valzasina, Gianluca Rotta, Francesca Granucci, Paola Ricciardi-Castagnoli

Research output: Contribution to journalArticlepeer-review

Abstract

Toll-like receptor 4 (TLR4) has been recently associated with cellular responses to lipopolysaccharide (LPS), and mice mutated in tlr4, such as C57BL/10ScCr or C3H/HeJ mice, become hyporesponsive to LPS. In this study, we have analyzed the capacity of bone marrow-derived dendritic cells (BMDC) from C57BL/10ScCr (ScCr-BMDC) or C3H/HeJ (HeJ-BMDC) mice to respond to LPS or to Gram-negative bacteria. We show that ScCr- or HeJ-BMDC are insensitive to LPS, but can mature in response to live and killed Gram-negative bacteria. Interestingly, only ScCr-BMDC but not HeJ-BMDC, stimulated with bacteria, have reduced capacity to produce pro- and anti-inflammatory cytokines as compared to BMDC from control mice, probably due to genetic defects unrelated to the tlr4 mutation. Nevertheless, ScCr-BMDC and ScCr BM-macrophages (BM-MΦ) phagocytose Salmonella typhimurium similarly to control cells, indicating that TLR4 is not compulsory for bacterial uptake. Moreover, BM-MΦ, but not BM-DC from B10ScCr or C3H/HeJ mice, are impaired in their capacity to kill intracellular bacteria and to produce NO as compared to wild type controls. However, the bacteria killing property of BM-MΦ is completely restored by pretreating the cells with IFN-γ. Hence, TLR4 plays different roles in DC versus MΦ.

Original languageEnglish
Pages (from-to)2800-2806
Number of pages7
JournalEuropean Journal of Immunology
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 2002

Keywords

  • Dendritic cell
  • LPS
  • Nitric oxide
  • Salmonella typhimurium
  • TLR4

ASJC Scopus subject areas

  • Immunology

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