286 Ó 2011 John Wiley & Sons A/S • Immunological Reviews 240/2011 Evelyne Mougneau Franck Bihl Nicolas Glaichenhaus Cell biology and immunology of Leishmania Authors’ addresses Evelyne Mougneau 1,2 , Franck Bihl 3 , Nicolas Glaichenhaus 1,2 1 Institut National de la Sante ´ et de la Recherche Me ´dicale, University of Nice-Sophia Antipolis, Valbonne, France. 2 Institut de Pharmacologie Mole ´culaire et Cellulaire, Valbonne, France. 3 Centre National de la Recherche Scientifique, UMR6097, University of Nice-Sophia Antipolis, Institut de Pharmacologie Mole ´culaire et Cellulaire, Valbonne, France Correspondence to: Nicolas Glaichenhaus Institut de Pharmacologie Mole ´culaire et Cellulaire U924, 660 Route des Lucioles 06560 Valbonne France Tel.: +33 4 93 95 77 85 Fax: +33 4 93 95 77 08 e-mail: nicolas.glaichenhaus@unice.fr Acknowledgements The authors declare no conflicts of interest. Immunological Reviews 2011 Vol. 240: 286–296 Printed in Singapore. All rights reserved Ó 2011 John Wiley & Sons A/S Immunological Reviews 0105-2896 Summary: More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellu- lar protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, respectively. This infectious disease model was later used to identify and assess the role of key factors, such as interleukin-12 (IL-12) and IL-4, in Th1 and Th2 maturation. While infection by Leishmania remains a popular model for immunologists who wish to assess the role of their favorite molecule in T-cell differentiation, other investigators have tried to better understand how Leishmania interact with its insect and mammalian hosts. In this review, we discuss some of these new data with an emphasis on the early events that shape the immune response to Leishmania and on the immune evasion mechanisms that allow this parasite to avoid the development of sterilizing immunity and to secure its transmission to a new host. Keywords: protozoa, innate immunity, adaptive immunity, immune evasion, vaccine Introduction The obligate kinetoplastid protozoan parasites of the genus Leishmania are spread by sand fly vectors and cause a spectrum of diseases collectively known as leishmaniasis that range from self-healing cutaneous lesions to fatal visceral leishmaniasis. Leishmaniasis is prevalent in tropical and subtropical regions of the world and endemic in 88 countries, with two million new cases reported annually. Leishmania have a dimorphic life cycle: extracellular stage promastigotes multiply and develop within the digestive tract of sand flies, and intracellular amastigotes reside and multiply within the phagolysosomal vacuoles of mammalian phago- cytes. In the first part of this review, we discuss a few recent papers that have provided new information on the interaction of Leishmania promastigotes with its sand fly host and on the evolutionary mechanisms that have allowed this parasite to adapt to new ecological niches, vectors, and hosts. When infected sand flies bite a mammalian host, metacyclic prom- astigotes are injected into the skin where they are captured by phagocytic cells. Promastigotes then metamorphose to amastigotes that multiply and are eventually released within