Identification of TLR inducing Th1-responsive Leishmania donovani amastigote-specific antigens

Abstract

Leishmania is known to elicit Th2 response that causes leishmaniasis progression; on the other hand, Th1 cytokines restricts amastigote growth and disease progression. In this study, we report the potential of two leishmanial antigens (65 and 98 kDa, in combination) which enhance strong macrophage effector functions, viz., production of respiratory burst enzymes, nitric oxide, and Th1 cytokines. The identification of antigens were done by resolving the crude soluble antigens on SDS-PAGE and eluted by reverse staining method. Further, RAW264.7 macrophages were challenged with eluted antigens, and the innate immune response was observed by detecting respiratory burst enzymes, nitric oxide (NOx), TNF-α, IFN-γ, IL-12, toll-like receptors (TLRs) gene expression, and TLR-signaling proteins. These antigens increased the production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, NOx, TNF-α, IFN-γ, IL-12, TLR2, and p38 mitogen-activated protein kinase. These antigens also induced human peripheral blood mononuclear cells proliferation and Th1 cytokine production. This study concludes that these antigens induce innate immune response as well as have prophylactic efficacy.

Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver

“…Such factors may include the specific ligand (e.g., the pathogen), pathogen or ligand interaction with other recognition or accessory receptors (71,78), effects of the initially provoked host response, or the duration (68) and/or timing of receptor engagement (see above). In the case of L. donovani amastigotes, little is known about possible parasite ligands for either TLR2 or TLR4 (72), although amastigote-derived antigens reportedly induce TLR2 mRNA expression in vitro (73).…”

Toll-Like Receptors inLeishmaniaInfections: Guardians or Promoters?

“…For example, two antigens isolated from L. donovani amastigotes were shown to upregulate TLR2 expression in RAW264 macrophages [49]. The 65 and 98 kDa proteins induced elevated levels of MAPK p38, as well as its phosphorylation in relation to that of ERK1/2, leading the authors to conclude that they induced the activation of TLR signaling proteins.…”

Leishmania donovani influenced cytokines and Toll‐like receptors expression among Sudanese visceral leishmaniasis patients

“…Toll‐like receptors initiate innate responses in a variety of ways, leading to the production of inflammatory cytokines by macrophages . The TLR signalling activates macrophage effectors functions and could lead to either Th1 or Th2 response depending upon the nature of parasitic molecules . Leishmania employs various survival strategies to subvert the proinflammatory response generated by the host macrophages .…”