Dendritic cells in Leishmania major infections: mechanisms of parasite uptake, cell activation and evidence for physiological relevance

Abstract

Leishmaniasis is one of the most important infectious diseases worldwide; a vaccine is still not available. Infected dendritic cells (DC) are critical for the initiation of protective Th1 immunity against Leishmania major. Phagocytosis of L. major by DC leads to cell activation, IL-12 release and (cross-) presentation of Leishmania antigens by DC. Here, we review the role of Fcγ receptor- and B cell-mediated processes for parasite internalization by DC. In addition, the early events after parasite inoculation that consist of mast cell activation, parasite uptake by skin-resident macrophages (MΦ), followed by neutrophil and monocyte immigration and DC activation are described. All these events contribute significantly to antigen processing in infected DC and influence resulting T cell priming in vivo. A detailed understanding of the role of DC for the development of efficient anti-Leishmania immunity will aid the development of potent anti-parasite drugs and/or vaccines.

In vivo Confocal Microscopy Features of Cutaneous Leishmaniasis

“…Cutaneous infection by Leishmania organisms results from the introduction of promastigotes into the skin from the bite of a sandfly of the subfamily Phlebotominae. After inoculation of infectious-stage metacyclic promastigotes into the upper dermis by the bite of a sandfly, Leishmania primarily locate to the phagolysosomes of skin-resident macrophages where the parasite transforms to obligate intracellular amastigotes and replicates [4]. Release of free amastigotes into the tissue leads to infection of other phagocytes.…”

Immune responses against protozoan parasites: a focus on the emerging role of Nod-like receptors

“…More importantly, activation of TLR2, TLR4, or TLR9 by their respective antigens results in significant protection from Leishmania pathogenesis and parasite burden [77]. Additionally, the results of recent studies show a surprising role for eosinophils and mast cells in inducing proper immune responses against Leishmania and in providing protection, mostly through the regulation of DCs and adaptive immunity [78,79]. …”

The Roles of Mast Cells in Parasitic Protozoan Infections

“…After L. major inoculation, MC activation and parasite uptake by skin-resident Mφ occurred, followed by neutrophil and monocyte immigration and DC activation. Therefore, MC-dependent recruitment of Mφ, PMN, and DC to the skin is involved in controlling leishmaniasis (66). Furthermore, using MC-deficient Kit W-sh / Kit W-sh mice for infection with L. major promastigotes results in a worse disease outcome, e.g., significantly enhanced lesion progression and lesional parasite burdens, accompanied by significantly decreased levels of IFN-γ and IL-17A, but significantly increased IL-4 and IL-10, compared to wild-type mice, indicating that MCs play a crucial role against Leishmania parasites by promoting Th1 and Th17 responses in vivo (26).…”