leishmaniasis
Leishmaniasis is one of the neglected tropical, vector-borne diseases
which is widely spread in tropical and certain subtropical
areas[38], [39]. The poorest people with malnutrition,
population displacement, weak immune system, poor housing, and lack of
financial resources are affected more by this disease. According to the
world health organization, around 700 000 to 1 million new cases occur
annually. Leishmaniasis is caused by an intracellular flagellated
Trypanosomatid protozoan parasite that belongs to the genusLeishmania [40], [41]. These parasites are
transmitted by infected phlebotomine female sand fly bites[40].
Around 20 Leishmania species are identified as pathogenic to
humans which are transmitted by around 30 species of phlebotomine
sandflies[40], [41]. Leishmania parasites have a
digenetic lifecycle where they spend the flagellated promastigote form
inside the sand fly which is the vector, and the non-flagellated
amastigote form inside the mammalian host[42], [43]. Inside the
mammalian host, Leishmania mainly infects host
macrophages[44]. Upon entering into macrophages, to ensure its
stabilization and survival against macrophage’s defense responses such
as immune activation, oxidative stress, and apoptosis, theLeishmania parasite modulates the host macrophage in such a way
that it can overcome the host immune response against the
infection[8], [13], [44].
Leishmaniasis is clinically classified into three forms, namely;
cutaneous leishmaniasis (CL), visceral leishmaniasis (VL), and
mucocutaneous leishmaniasis (MCL) which is caused by the replication of
the infected parasite in macrophages in the dermis, reticuloendothelial
system, dermis, and naso-oropharyngeal mucosa, respectively [40],
[41], [45]. When the macrophage is full of parasites within its
hold, the host cell bursts and releases the parasites that will go and
infect the neighboring macrophages[40]. Untreated VL can cause
life-threatening systemic infection while CL can cause chronic skin
sores. Facial disfigurement and life-threatening destruction of
nasopharyngeal mucosa can be caused by the MCL[46]. Multiple species
of the genus Leishmania cause CL: L. tropica, L. major, L.
aethiopica, L. infantum, and L. donovani in the old world (Africa,
Asia, and Europe), and L. mexicana, L. amazonensis and L.
braziliensis in the new world [41], [46]. Moreover, many
intracellular pathogens like Leishmania can interact and hijack
cellular organelles like endoplasmic reticulum (ER) for their survival
and replication, triggering the ER stress and subsequently ER stress
response [7], [8]