Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans

Abstract

SUMMARYLymphocytes ofindivlduals from a country non-endemic for Leishmania (Sweden), responded wiih a vigorous interferon-gamma (IFN--/) and IL-6 response when exposed to live or dead promastigotcs of Leishmania aethiopica. This response was sometimes as strong as when the same cells were exposed lo the mitogen (phytohaetnaggluiinin (PMAl). Furthermore, supernatants of cells exposed to Leishmania promastigotcs were able to inhibit the amastigote form of the same parasite, ln some few instances there was no such reactivity to Leishmania parasites, [t is proposed that most individuals have such a first line cytokine response which is enough to prevent further spread and growth of lhe parasites. In exposed individuals who display disease symptoms, this non-Leishniania-specific response is overcome (by dose) or is weak (for genetic reasons). In the latter instances curbing of parasite growth would depend on acquired immunity.

Natural killer cells and the biology of parasitism

“…NK cells from unexposed human donors proliferate and secrete IFN- in response to Leishmania antigen (Akuffo and Britton, 1992;Maasho et al, 1998;Nylen et al, 2004). NK cell secreted IFN- is thought to increase macrophage-mediated killing of intracellular parasites and to trigger Th1 immune response.…”

Natural and acquired resistance toLeishmania: cellular activation byLeishmania aethiopicaof mononuclear cells from unexposed individuals is through the stimulation of natural killer (NK) cells

“…A possible reason for our initial 5ndings oT in vitro cellular reactivity of normal cells to an antigen ihcy had never encoun-tered in riro [ 13] could have been because the antigen being used for stimulation may have had superanligcn-likc properties. Superanligens are molecules that are stimulator) lor T lymphocyles by cross-linking variable parts of their antigen receptors (on !/(• T cells of the/i-chain) with MHC class II molecules on accessory cells [26].…”

“…aethiopica hy IFN-y production [13) or proliferation [14,15], We have been interested in what antigens or material the cells from these individuals are responding to. and have excluded the possibility of the response i^eing due to the presence of endotoxin in our antigen preparations [13], Furthemore.…”

“…and have excluded the possibility of the response i^eing due to the presence of endotoxin in our antigen preparations [13], Furthemore. since the ability to respond to L. aethiopica was not observed in all cases [13], the reactivity being measured is unlikely lo be due to classical mitogenic components of the antigen preparations.…”

Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis

“…Cytokines secreted by Lei.shmania-TcacUvc cells in unexposed individuals may eontribute to the primary protection against parasite invasion of macrophages in human Leishmania infections [28].…”