Investigating immune responses to parasites using transgenesis

Abstract

Parasites comprise diverse and complex organisms, which substantially impact human and animal health. Most parasites have complex life-cycles, and by virtue of co-evolution have developed multifaceted, often life-cycle stage-specific relationships with the immune system of their hosts. The complexity in the biology of many parasites often limits our knowledge of parasite-specific immune responses, to in vitro studies only. The relatively recent development of methods to stably manipulate the genetic make-up of many parasites has allowed a better understanding of host-parasite interactions, particularly in vivo. In this regard, the use of transgenic parasites can facilitate the study of immunomodulatory mechanisms under in vivo conditions. Therefore, in this review, we specifically highlighted the current developments in the use of transgenic parasites to unravel the host's immune response to different life-cycle stages of some key parasite species such as Leishmania, Schistosoma, Toxoplasma, Plasmodium and Trypanosome and to some degree, the use of transgenic nematode parasites is also briefly discussed.

Keywords: Immune response; In vivo; Parasites; Transgenesis.

Fig. 1

A flow diagram for the identification and screening of research articles for the current review

Fig. 2

The site of OVA expression inside the transgenic parasite has influenced the cellular immune responses in which cytosolic OVA leads to stimulation of CD4⁺ T cells and IFN-γ production. To confirm whether OVA expressing transgenic T. gondii can induce T cell proliferation, CD4⁺ T cells were labelled with CFSE and the in vitro response of the cells showed the cytosolic OVA failed to show any T cell response, but OVA expressed at the parasitophorous vacuole induced T cell proliferation [25]

Fig. 3

The expression of two OVA epitopes (NT-OVA and SP-OVA) in L. major parasite showed different type of T cell responses when exposed to dendritic cells and macrophages in vitro separately. Whereas, injection of both OVA epitope transgenic parasites into mice after adoptive transfer of OVA specific OT-I T cells showed only an induction of CD8⁺ T cells in vivo

Fig. 4

Transgenic P. berghei parasite expressing a circumsporozoite protein induces a strong antibody production and protection efficiency. Briefly, the transgenic malaria parasite lines infect the RBC of C57BL/6 mice and leads to the activation of B cells and IFN-γ production by CD4⁺ T cells. Passive transfer of antibodies to naïve recipient mice confers protection through opsonization process

Fig. 5

Expression of flagellar protein PAR4 in T. cruzi causes the activation of macrophages, CD8⁺ T cells and NKT cells which leads to the high rate of parasite destruction from the circulation through the production of different cytokines having direct effect such as TNF-a and through the activation of plasma cells and production of protective antibodies

Fig. 6

Schistosoma mansoni eggs transduced with lentiviruses containing shRNAmir showed a significant reduction the size of granuloma comparing with the untraduced eggs [8] and the expression of chicken ovalbumin in S. mansoni eggs after delivery of the OVA transgene through the lentiviral transduction system leads in to the recognition of the OVA by OT-II T cells in vitro