Abstract
BackgroundThe Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. Symptomatic leishmaniasis causes considerable human morbidity in endemic regions. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment. MSP is a metalloprotease encoded by a tandem array of genes belonging to three msp gene classes, whose mRNAs are differentially expressed in different life stages of the parasite. Like other cells, Leishmania spp. release small membrane-bound vesicles called exosomes into their environment. The purpose of this study was to detect MSP proteins in exosomal vesicles of Leishmania spp. protozoa.MethodsUsing mass spectrometry data we determined the profile of MSP class proteins released in L. infantum exosomes derived from promastigotes in their avirulent procyclic (logarithmic) stage and virulent stationary and metacyclic stages. MSP protein isoforms belonging to each of the three msp gene classes could be identified by unique peptides.ResultsMetacyclic promastigote exosomes contained the highest, and logarithmic exosomes had the lowest abundance of total MSP. Among the MSP classes, MSPC class had the greatest variety of isoforms, but was least abundant in all exosomes. Nonetheless, all MSP classes were present at higher levels in exosomes released from stationary or metacyclic promastigotes than logarithmic promastigotes.ConclusionsThe data suggest the efficiency of exosome release may be more important than the identity of MSP isoform in determining the MSP content of Leishmania spp. exosomes.
Highlights
The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin
Studies of L. infantum show that the abundance of major surface protease (MSP) increases approximately 14-fold while the parasite develops from a non-infectious logarithmic growth stage to an infectious metacyclic stage in vitro [7]
Recognizing the likely importance of exosomes and of MSPs in pathogenesis of leishmaniasis, the purpose of this study was to compare the abundance and the isoforms of MSP in exosomes released by L. infantum promastigotes in their different life-cycle stages, including the non-infective logarithmic and the infective stationary growth stages, and from infectious metacyclic promastigotes purified from stationary L. infantum promastigotes
Summary
The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment. The extracellular promastigote of Leishmania spp. displays an abundant major surface protease (MSP, called GP63), a virulence factor that promotes parasite survival both intracellularly, through modulating macrophage killing mechanisms, and extracellularly by evading microbicidal proteins [5]. The process of parasite differentiation in the sand fly vector from procyclic to metacyclic forms is pre-adaptive to infection of a mammal host [6]. Studies of L. infantum show that the abundance of MSP increases approximately 14-fold while the parasite develops from a non-infectious logarithmic growth stage to an infectious metacyclic stage in vitro [7]
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