Leishmania species-dependent functional duality of toll-like receptor 2

IUBMB Life. 2019 Nov;71(11):1685-1700. doi: 10.1002/iub.2129. Epub 2019 Jul 22.

Abstract

Toll-like receptors (TLRs) are a subset of pattern recognition receptors (PRR) in innate immunity and act as a connecting link between innate and adaptive immune systems. During Leishmania infection, the activation of TLRs influences the pathogen-specific immune responses, which may play a decisive role in determining the outcome of infection, toward elimination or survival of the pathogen. Antigen-presenting cells (APCs) of the innate immune system such as macrophages, dendritic cells (DCs), neutrophils, natural killer (NK) cells, and NKT cells express TLR2, which plays a crucial role in the parasite recognition and elicitation of immune responses in Leishmania infection. Depending on the infecting Leishmania species, the TLR2 pathways may result in a host-protective or a disease-exacerbating response. While Leishmania major and Leishmania donovani infections trigger TLR2-related host-protective and non-protective immune responses, Leishmania mexicana and Leishmania infantum infections are reported to elicit TLR2-mediated host-protective responses and Leishmania amazonensis and Leishmania braziliensis infections are reported to evoke a disease-exacerbating response. These findings illustrate that TLR2-related effector functions are diverse and may be exerted in a species- or strain-dependent manner. TLR2 agonists or antagonists may have therapeutic potentials to trigger the desired immune response during leishmaniasis. In this review, we discuss the TLR2-related immune responses during leishmaniasis and highlight the novel insights into the possible role of TLR2-driven resistance or susceptibility to Leishmania.

Keywords: Leishmania; TLR2; immune response; resistance; susceptibility.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiparasitic Agents / pharmacology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / parasitology
  • Drug Resistance, Neoplasm*
  • Host-Parasite Interactions / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Leishmania / immunology*
  • Leishmaniasis / immunology*
  • Leishmaniasis / parasitology
  • Macrophages / immunology
  • Macrophages / parasitology
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 2 / immunology*

Substances

  • Antiparasitic Agents
  • Cytokines
  • Toll-Like Receptor 2