UPR triggered by leishmaniasis
Numerous studies have been done to assess the activated UPR in
leishmaniasis caused by different Leishmania species, mainly,Leishmania braziliensis , Leishmania infantum, Leishmania
donovani, and Leishmania amazonensis [1], [7], [47],
[48].
The role of IRE1/XBP1-splicing arms of the UPR is well documented in
viral and bacterial infections but poorly reported in protozoan
parasitic infections. In an attempt to investigate the role of ER stress
during Leishmania amazonensis infection, Dias-Teixeira et
al . group demonstrated that, upon infection by Leishmania
amazonensis , the IRE1-XBP1 branch of UPR gets activated to overcome the
cellular oxidative stress and leads to up-regulation of IFN-1β which
helps in establishment of infection and its pathogenesis [47].
Induction of IFN-1β expression in Leishmania amazonensisinfection is dependent on Toll-Like Receptor 2 (TLR2) activation, which
is a pattern recognizing receptor and IFN-1β appears to favorLeishmania amazonensis parasite growth[49]. Further studies
by this group have shown that ER-stress response enhancesLeishmania amazonensis infection in IFN-1 dependent manner.Leishmania amazonensis activates ER stress response by inducing
the IRE1-XBP1 branch which subsequently leads to the splicing of XBP1
and nuclear translocation. By knocking down the expression of XBP1, they
observed a reduction in infection mediated by the reduction of IFN-1β.
Furthermore, down-regulation of heme oxygenase (HO) and an increase in
cellular Nitric Oxide (NO) concentration were also reported when the
XBP1 was knocked down. These experimental data collectively suggest that
XBP1 is critical for Leishmania amazonensis growth in infected
macrophages and the promotion of Leishmania amazonensis infection
by XBP1 is dependent on IFN-1β[47]. With all the data available up
to date, the study group has proposed a model which deciphers the role
of XBP1 during Leishmania amazonensis infection as shown in
figure 4 and 5.