Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans

Elisabetta Blasi, Anna Mucci, Rachele Neglia, Francesco Pezzini, Bruna Colombari, Danuta Radzioch, Andrea Cossarizza, Enrico Lugli, Gianfranco Volpini, Giuseppe Del Giudice, Samuele Peppoloni

Research output: Contribution to journalArticle

Abstract

The aim of this study was to assess the role of TLR2, TLR4 and MyD88 accessory molecule in the effector and secretory response of macrophages to viable microbial agents. Using TLR-deleted macrophage cell lines generated from the bone marrow of genetically engineered mice (TLR4 gene-deficient, MyD88- and TLR2-knockout mice) and wild-type control mice, we found that TLR2-deleted macrophages exhibit increased ability to contain Candida albicans infection compared to TLR2+/+ counterpart. In contrast, both MyD88-/- and TLR4-/- macrophages retain levels of functional activity comparable to that of the respective wild-type MyD88+/+ and TLR4+/+ controls. The difference in anticandidal effector functions observed between TLR2-/- and TLR2+/+ macrophages is abrogated upon opsonization of the fungal target and interestingly is not observed when using other microbial targets, such as Streptococcus pneumoniae and Helicobacter pylori. When tested for secretory response to C. albicans, TLR2-deleted macrophages show a pattern of cytokine production similar to that of TLR2+/+ controls. Finally, flow cytometry analysis reveals that TLR2-deleted macrophages express only TLR4, while, as expected, TLR2+/+ macrophages are both TLR2 and TLR4 positive; in no cases, modulation of such markers occurs in macrophages exposed to C. albicans infection. In conclusion, these data indicate that TLR2 and TLR4 have different biological relevance, in which TLR2 but not TLR4, is involved in the accomplishment of macrophage-mediated anticandidal activity, while the secretory response to C. albicans appears to be TLR4 but not TLR2-dependent.

Original languageEnglish
Pages (from-to)69-79
Number of pages11
JournalFEMS Immunology and Medical Microbiology
Volume44
Issue number1
DOIs
Publication statusPublished - Apr 1 2005

Keywords

  • Antimicrobial activity
  • Candida albicans
  • Macrophages
  • Toll-receptors

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Infectious Diseases

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    Blasi, E., Mucci, A., Neglia, R., Pezzini, F., Colombari, B., Radzioch, D., Cossarizza, A., Lugli, E., Volpini, G., Del Giudice, G., & Peppoloni, S. (2005). Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans. FEMS Immunology and Medical Microbiology, 44(1), 69-79. https://doi.org/10.1016/j.femsim.2004.12.005