Abstract
Infections with parasites of the genus Leishmania lead to a rapid, but transient activation of natural killer (NK) cells. In mice activation of NK cells requires a toll-like-receptor 9-dependent stimulation of dendritic cells (DC) which is followed by the production of IL-12. Although NK cells appear to be non-essential for the ultimate control of cutaneous and visceral leishmaniasis (VL) and can exhibit immunosuppressive functions, they form an important source of interferon (IFN)-γ, which elicits antileishmanial activity in macrophages and helps to pave a protective T helper cell response. In contrast, the cytotoxic activity of NK cells is dispensable, because Leishmania-infected myeloid cells are largely resistant to NK-mediated lysis. In human cutaneous and VL, the functional importance of NK cells is suggested by reports that demonstrate (1) a direct activation or inhibition of NK cells by Leishmania promastigotes, (2) the suppression of NK cell numbers or activity during chronic, non-healing infections, and (3) the recovery of NK cell activity following treatment. This review aims to provide an integrated view on the migration, activation, inhibition, function, and therapeutic modulation of NK cells in experimental and human leishmaniasis.
Highlights
Infections with parasites of the genus Leishmania lead to a rapid, but transient activation of natural killer (NK) cells
This review aims to provide an integrated view on the migration, activation, inhibition, function, and therapeutic modulation of NK cells in experimental and human leishmaniasis
Independent of the question whether NK cells are essential or dispensable for the control of Leishmania parasites, there is convincing evidence for a protective function of NK cells in mouse CL, which is mainly based on the IFN-γ-mediated activation of macrophages and development of Th1 cells
Summary
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Bavaria, Germany. Depending on the parasite subgenus [subgenus Leishmania (L.) vs Viannia (V.)], species and strain, the dose of transmitted parasites, the inoculation site and the quality of the immune response of the infected host, the infection can remain asymptomatic, or turn into a diverse set of clinical disease manifestations. These include local cutaneous leishmaniasis (LCL), diffuse cutaneous leishmaniasis (DCL), disseminated cutaneous leishmaniasis, mucocutaneous or mucosal leishmaniasis (MCL) as well as visceral leishmaniasis (VL) (Murray et al, 2005). Both in the subcutaneous (s.c.) footpad and the intradermal (i.d.) ear-infection model inoculation of small or high numbers of parasites leads to non-ulcerative or ulcerative dermal lesions, which in several mouse strains closely reflect the self-healing skin lesions observed in patients with LCL
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