Chronic infection by Leishmania amazonensis mediated through MAPK ERK mechanisms
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IMMUNOLOGY AT THE UNIVERSITY OF IOWA
Chronic infection by Leishmania amazonensis mediated through MAPK ERK mechanisms Pedro A. Martinez • Christine A. Petersen
Christine A. Petersen Ó Springer Science+Business Media New York 2014
Abstract Leishmania amazonensis is an intracellular protozoan parasite responsible for chronic cutaneous leishmaniasis (CL). CL is a neglected tropical disease responsible for infecting millions of people worldwide. L. amazonensis promotes alteration of various signaling pathways that are essential for host cell survival. Specifically, through parasite-mediated phosphorylation of extracellular signal regulated kinase (ERK), L. amazonensis inhibits cell-mediated parasite killing and promotes its own survival by co-opting multiple host cell functions. In this review, we highlight Leishmania-host cell signaling alterations focusing on those specific to (1) motor proteins, (2) prevention of NADPH subunit phosphorylation impairing reactive oxygen species production, and (3) localized endosomal signaling to up-regulate ERK phosphorylation. This review will focus upon mechanisms and possible explanations as to how Leishmania spp. evades the various layers of defense employed by the host immune response. Keywords Leishmania Extra cellular signal regulated kinase (ERK) MAPK NADPH oxidase Reactive oxygen species (ROS)
Introduction Leishmania infection importance: epidemiology Leishmania spp. are obligate intracellular parasites in the family Trypanosomatidae. They are the causative agents of the spectral disease, leishmaniasis. Leishmaniases are neglected tropical diseases transmitted by infected sandflies. Sandflies belong to either Lutzomyia (New World) or Phlebotomus (Old World) geneses. There are roughly 30 documented species of Leishmania, with 20 of these able to cause disease in humans. Currently, approximately 12
P. A. Martinez C. A. Petersen (&) Department of Epidemiology, College of Public Health, University of Iowa, S429 CPHB, 145 Riverside Drive, Iowa City, IA 52242, USA e-mail: [email protected] P. A. Martinez C. A. Petersen Immunology Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
million people are infected worldwide, which makes Leishmaniasis a global issue, affecting individuals in 98 countries. The disease is responsible for roughly 70,000 deaths per year [1], most of these attributed to the visceralizing form of the disease. In the few past years, we have seen a rise in canine visceral leishmaniasis (VL) [2] in the US, as well as in Europe. This places Leishmaniasis within the coasts of the most industrialized nations in the world and is no longer a solely a problem in third world countries. While we currently do not know of any reported VL cases transmitted from a canine to a human in the US, because of the proximity of infected canines, with immunocompromised and other individuals, the possibility is always there [3]. Cutaneous leishmaniasis (CL) is defined as disease caused by Leishmania spp. and leads to an ulcera
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