Cutaneous leishmaniasis caused by Leishmania parasites produces a wide range of clinical manifestations. Although the parasites influence disease severity, cytolytic CD8 T-cell responses also contribute to disease pathology.
The talk explored findings showing that, although these responses originate in the lymph nodes, expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8 T cells in Leishmania-infected mice. This suggested that local signals within inflamed skin induced cytolytic function.
The research also found that Leishmania-infected lesions were hypoxic and that neutrophil recruitment caused this hypoxia. Notably, hypoxia within the infected skin promoted granzyme B expression in CD8 T cells, resulting in more severe disease. The findings suggested that targeting hypoxia-driven signals supporting the local differentiation of cytolytic CD8 T cells could improve outcomes for patients with cutaneous leishmaniasis and other inflammatory skin diseases in which these cells contribute to pathogenesis.
About the Speaker
Dr Fernanda Novais was born in Brazil, a country where cutaneous leishmaniasis is endemic, and she has studied immunity to cutaneous leishmaniasis in mice and humans for over 20 years. Dr. Novais’ discoveries have led to (i) an understanding of how neutrophil-macrophage crosstalk promotes Leishmania killing, (ii) the identification of monocyte subsets responsible for parasite control, and (iii) a new paradigm in which CD8 T cells are pathogenic rather than protective in cutaneous leishmaniasis. Her lab is currently focused on understanding how the environmental signals from the Leishmania-inflamed skin dictate the function of immune cells.
