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Schematic representation of the physiological roles of Leishmania RCD. In the sand fly vector, Leishmania RCD allows a limited number of parasites, among the fittest, to continue the cell cycle, which is of particular interest because of the limited resources within the vector digestive tract. In the mammalian host, Leishmania RCD induces elimination of damaged/unfit cells, inhibition of the secretion of pro-inflammatory molecules and, on the contrary, secretion of anti-inflammatory molecules by the infected macrophage, inhibition of parasite antigen presentation, and activation of the macrophage autophagy machinery which negatively regulates T cell proliferation. Ultimately, this makes it possible to avoid hyperparasitism, to maintain Leishmania clonality, and to ensure survival of the fittest more virulent parasites. As a conclusion, Leishmania RCD appears as a selfish altruism, favoring transmission of the fittest parasites.
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