Recombinant Leishmania major lipophosphoglycan 3 activates human T-lymphocytes via TLR2-independent pathway

Abstract

Leishmaniasis is one of the most common infectious diseases transmitted by an obligate intracellular genus Leishmania. As there is no efficient vaccination strategy for leishmaniasis, new immunostimulatory components may enhance protective immune responses against this parasite. Lipophosphoglycan 3 (LPG3) is an essential protein required for LPG assembling. In this study, the ability of recombinant LPG3 (rLPG) and its fragments to activate isolated healthy human T-cells and cytokine secretion was evaluated in vitro. The results showed that rLPG3 and its N-terminal fragment (rNT-LPG3) enhanced expression of CD69 on the surface of T-cells and promoted differentiation of CD4 + T-lymphocytes toward a T-helper 1 (T H 1) phenotype, in part, through up-regulation of interferon (IFN)-expression in a TLR2-independent manner. These results indicated the protective effects of LPG3 (particularly NT-LPG3 fragment) as a potent immunostimulatory component of leishmania in vaccination against leishmaniasis. Further investigations in in vivo assays are clearly warranted.

A Non‐pathogenic Recombinant Leishmania Expressing Lipophosphoglycan 3 Against Experimental Infection with Leishmania infantum

“…The ER‐resident LPG3 chaperon molecule is thought to be essential for parasite infectivity and has the potential to direct the immune responses against the parasite as well . In our previous study, it was observed that immunization with the LPG3 DNA led to a significantly higher IFN‐ γ /IL‐10 ratio with no protective effect against infectious challenge with L. infantum .…”

Immune response to recombinant Leishmania infantum lipophosphoglycan 3 plus CpG oligodeoxynucleotides in BALB/c mice

“…GRP94 has been used as an immune adjuvant and/or peptide‐specific vehicle with viral and tumour antigens in vaccination studies to promote a Th1 immunity as well as CTL activity . With regard to high levels of homology of LPG3 to GRP94, this chaperon is found to have a potential role in directing the immune response of the host against the parasite by inducing both IFN‐γ‐producing CD4+ and CD8+ T cells …”