Innate Immune Responses Against Leishmania Parasites

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Background

Leishmaniasis are a group of vector-borne diseases caused by the protozoa Leishmania. These neglected diseases are endemic in more than 90 countries, with over 2 million new cases reported every year. Clinical manifestations range from limited cutaneous lesions to the fatal visceral leishmaniasis, depending mostly on the parasite species and the host immune system. There is no vaccine available and there is an urgent need of discovering new alternative therapies.

Leishmania parasites are injected into the host skin by the bite of an infected female sand fly, a feature frequently not considered by most experimental models. The rich inoculum delivered by the vector bite, composed by few parasites and factors/molecules derived from both Leishmania and sand fly, ensures the success of the infection. Vector bite gives rise to an inflammatory process, characterized by the rapid influx of innate cells to the site of infection. Additionally, parasites encounter in the host skin a variety of resident innate immune and non-hematopoietic cells that can affect the outcome of the disease. To establish the infection, Leishmania efficiently evades the host microbicidal mechanisms and resides mostly within the vertebrate host macrophages. Protective immunity is achieved through the generation of IFN-y-producing Th1/Tc1 cells, capable of activating infected macrophages.

Undoubtedly, recruited innate immune cells, innate resident cells and non-hematopoietic cells directly impact the course of disease. However, there are still gaps in our knowledge on how these cells work during infection. Neutrophils and monocytes, for instance, are recruited early to the site of infection and may act as permissive cells promoting the disease by unknown mechanisms. Yet, those observations diverge depending on the parasite species and experimental model. Unlike neutrophils and monocytes, the role of other innate immune cells during Leishmania infection is still underappreciated. Recent reports have shed light into how eosinophils, mast cells and even skin-resident stromal cells, such as keratinocytes and fibroblasts, might influence disease. Finally, we still need efforts to understand how, and which factors or molecules derived from the parasites and vector may influence innate immunity. In this Research Topic we intend to gather articles that bring new insights into the importance of the innate immune response during Leishmania infection. We welcome the submission of Original Research Articles on in vitro and in vivo studies, Review, Mini-Review, Hypothesis and Theory, and Perspective articles. Ideally the article should fit in one of the following topics:

1. Innate immune host cells-parasite cellular and molecular interactions in vitro and in vivo
2. Crosstalk between innate immune cells during Leishmania infection
3. Crosstalk between recruited innate immune cells and skin resident cells during infection
4. Skin non-hematopoietic cell response to parasites
5. Impact of vector or parasite-derived factors on innate immune cells
6. Mechanisms driving Leishmania evasion of innate immune response
7. The microbiome and host innate immune cells interface during Leishmania infection

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