Abstract
Kinetoplastid membrane protein-11 (KMP-11), a protein present in all kinetoplastid protozoa, is considered a potential candidate for a leishmaniasis vaccine. In Leishmania amazonensis, KMP-11 is expressed in promastigotes and amastigotes. In both stages, the protein was found in association with membrane structures at the cell surface, flagellar pocket, and intracellular vesicles. More importantly, its surface expression is higher in amastigotes than in promastigotes and increases during metacyclogenesis. The increased expression of KMP-11 in metacyclic promastigotes, and especially in amastigotes, indicates a role for this molecule in the parasite relationship with the mammalian host. In this connection, we have shown that addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide production. The doses of KMP-11, the IL-10 levels, and the intracellular amastigote loads were strongly, positively, and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10-neutralizing antibodies, but not by isotype controls. The neutralizing antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. All these data indicate that KMP-11 acts as a virulence factor in L. amazonensis infection.
Highlights
THE LEISHMANIASESDiversity is the key word for defining the leishmaniases, a group of diseases caused by the infection with parasitic protozoa of the genus Leishmania and transmitted by sandfly (Phlebotominae) vectors [1]: diversity of parasite species, diversity of vector species, diversity of eco-epidemiological conditions involved in transmission, and diversity of clinical presentations
Reviewed by: Marisa Mariel Fernandez, University of Buenos Aires, Argentina Celio Geraldo Freire De Lima, Federal University of Rio de Janeiro, Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
We have shown that addition of Kinetoplastid membrane protein-11 (KMP-11) exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide production
Summary
Diversity is the key word for defining the leishmaniases, a group of diseases caused by the infection with parasitic protozoa of the genus Leishmania and transmitted by sandfly (Phlebotominae) vectors [1]: diversity of parasite species, diversity of vector species, diversity of eco-epidemiological conditions involved in transmission, and diversity of clinical presentations. While Old World CL is caused by three species, all of them of the Leishmania subgenus, American tegumentary leishmaniasis, so called because it encompasses CL, DCL, and ML, can be caused by various species of the Leishmania and the Viannia subgenera, the latter been exclusive of the American continent. It is currently estimated an annual incidence of 0.2–0.4 and 0.7–1.2 million cases for VL and CL cases, respectively, with a tentative estimate of 20,000–40,000 deaths per year due to VL. CL has a wider geographical distribution, with the Americas, the Mediterranean basin, and western Asia being the most affected regions [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
