Redundant and regulatory roles for Toll-like receptors in Leishmania infection

Clin Exp Immunol. 2017 Nov;190(2):167-186. doi: 10.1111/cei.13014. Epub 2017 Aug 7.

Abstract

Toll-like receptors (TLRs) are germline-encoded, non-clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs has far-reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence co-stimulatory molecule expression and determinant selection by major histocompatibility complex (MHC) class II and MHC class I for cross-presentation. The signals delivered by the TCR-peptide-MHC complex and co-stimulatory molecules are indispensable for optimal T cell activation. In addition, the cytokines induced by TLRs can skew the differentiation of activated T cells to different effector T cell subsets. However, the potential of TLRs to influence adaptive immune response into different patterns is severely restricted by multiple factors: gross specificity for the molecular patterns, lack of receptor rearrangements, sharing of limited number of adaptors that assemble signalling complexes and redundancy in ligand recognition. These features of apparent redundancy and regulation in the functioning of TLRs characterize them as important and probable contributory factors in the resistance or susceptibility to an infection.

Keywords: Leishmania; Macrophage; Pathogen associated molecular patterns (PAMP); Phagolysosome; Toll-like Receptors (TLRs).

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cross-Priming
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Leishmania / immunology*
  • Leishmaniasis / immunology*
  • Mice
  • Pathogen-Associated Molecular Pattern Molecules / immunology
  • Phagocytosis
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology
  • Toll-Like Receptors / classification
  • Toll-Like Receptors / deficiency
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology*

Substances

  • Pathogen-Associated Molecular Pattern Molecules
  • Toll-Like Receptors