Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induce cytolytic function. We recently found that Leishmania-infected lesions are hypoxic, and that the recruitment of neutrophils causes hypoxia. Notably, the hypoxic state of the infected skin results in the expression of granzyme B in CD8 T cells, resulting in more severe disease. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T 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.