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About the Authors:
Nilda E. Rodríguez
* E-mail: [email protected]
Affiliations Veterans' Affairs Medical Center, Iowa City, Iowa, United States of America, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America
Upasna Gaur Dixit
Affiliations Veterans' Affairs Medical Center, Iowa City, Iowa, United States of America, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America
Lee-Ann H. Allen
Affiliations Veterans' Affairs Medical Center, Iowa City, Iowa, United States of America, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America, Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America
Mary E. Wilson
Affiliations Veterans' Affairs Medical Center, Iowa City, Iowa, United States of America, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America, Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America, Department of Epidemiology, University of Iowa, Iowa City, Iowa, United States of America
Introduction
The Leishmania spp. are pathogenic protozoa that cause endemic human disease in tropical and subtropical countries. Leishmania transform between two distinct life cycle stages, the infective promastigote and the intracellular amastigote. During a blood meal, a sand fly vector inoculates promastigotes into the skin of the mammalian host, whereupon they are taken up by macrophages and convert into amastigotes. Amastigotes replicate intracellularly and spread to new macrophages, disseminating and causing disease [1], [2].
Many studies of Leishmania phagocytosis have addressed the interactions between macrophages and promastigotes. The promastigote surface metalloprotease GP63 (also called MSP) facilitates parasite entry through the third complement receptor CR3, which binds iC3b and mediates pathogen uptake without eliciting robust microbial responses [1], [3], [4]. Amastigotes have been shown to enter macrophages after ligating Fc-γ and phosphatidylserine (PS) receptors which induce TGF-β and IL-10 production, resulting in decreased classical macrophage activation and enhanced parasite survival [5], [6].
We previously showed that phagocytosis of Leishmania proceeds through a subset of lipid-enriched membrane microdomains called caveolae, which are enriched in cholesterol, ganglioside M-1 (GM-1), GPI anchored proteins and caveolins-1, -2 and -3 [7]–[9]. Leishmania infantum chagasi infection increases the abundance of transcripts encoding several proteins of caveolae, including dynamin-2 and caveolins-1 and -3 [10]. Furthermore, the caveolae markers GM-1 and caveolin-1 [7]–[9]...