life cycle of leishmania sp

8/9/2019 Life Cycle of Leishmania Sp

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Life Cycle of Leishmania

Life Cycle of Leishmania

Leishmania species all follow the same general life cycle pattern (Figure 1).

The parasite has two main morphological forms, termed amastigotes and

promastigotes, which are found in the mammalian and sandfly hosts

respectively. Amastigotes are amongst the smallest of eukaryotic cells, beingovoid cells of 35 mm on the mainaxis. They possess a nonfunctional flagellum,which does not project beyond the cell body, and are not capable of movement.The base of the flagellum originates in the flagellar pocket, a specializedinfolding of the surface membrane. The nucleus is centrally located and adjacent

to the smaller kinetoplast. About 10% of the total cellular DNA is found in thekinetoplast, the remainder in the nucleus. Promastigotes are larger andelongated, with a cell body length of 515 mm. The flagellum is functional in

promastigotes, projecting from the flagellar pocket to extend beyond the cellbody, and these are active motile forms. The flagellum is at the anterior end ofthe cell, its motion pulling the cell body along behind.

Amastigotes are largely intracellular stages that live in the phagolysosomalsystem of macrophages. No other host cell type is used. However, macrophagesare themselves a heterogeneous group and different subpopulations are involvedin different types of clinical disease. For example, skin macrophages are

parasitized in the case of cutaneous leishmaniasis, whereas Kupffer cells in theliver are parasitized in visceral disease. Macrophages are phagocytic and readily

engulf amastigotes, followed by phagosome lysosome fusion. This microbialdefence mechanism is lethal to most foreign organisms, as it results in exposure

to an acidic pH of 4.55.5 and attack by a battery of lysosomal enzymes.However, Leishmania can survive this experience, and indeed thrive in this

environment. Within the phagolysosomal environment the parasites grow and

divide, such that an individual macrophage may eventually contain many tens ofamastigotes. There is no specific escape mechanism known, and probably inmost cases the host cell simply ruptures when it cannot accommodate any more

parasites, which are then taken up by further macrophagesThe mammalian phase of the life cycle is chronic, overt signs of disease

lasting from months to a lifetime. Even in human cases where clinical cure isachieved, either naturally through an immune response or by chemotherapy, itis doubtful that the parasite is completely eliminated. If a patient is subsequentlyimmunocompromised, for eg human immunodeficiency virus (HIV) infection, this

can lead to a reactivation of disease. The same applies to canine leishmaniasis,which is more difficult to treat than human infection, and where parasites are

also likely to persist even if clinical cure can be achieved. Wild mammals infectedwith Leishmania almost certainly remain so for life, usually with little overt signof disease, and provide a long-term source of infection for humans.

Transmission of disease is by female sandflies, which are widely distributed

through tropical, subtropical to temperate regions of the world (Lane, 1993). Ofthe 700 or so described species of phlebotomine sandfly, approximately 70 havebeen implicated in transmission of leishmaniasis. Female sandflies require a

bloodmeal to provide nutrients for egg production. The females are pool-feeders,that is they use their mouthparts to probe and slice through the surfacecapillaries of the skin, then imbibe blood from the wound. So, despite their small

size of 24 mm, the bite of a sandfly can be painful. Female sandflies acquire

the parasite if, during the course of feeding on an infected mammalian host,

Uttam Kr. Patra. 2007 1


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Life Cycle of LeishmaniaLeishmania-infected macrophages and/ or free amastigotes are liberated into thewound site. These are then taken up by the sandfly along with the bloodmeal.

Figure 1. Leishmania life cycle in mammalian hosts (upper) and in sandfly vectors (lower).

Mammalian stage: (1) delivery of infective promastigotes into mammalian skin by the bite of sandfly vector;(2) phagocytosis of promastigotes by a macrophage; (3) fusion of the phagosome containing a promastigote

with the lysosome; (4) differentiation of promastigote into amastigote in the phagolysosome of the infected

macrophage; (5) replication of an amastigote in a parasite-containing or parasitophorous vacuole; (6)formation of large parasitophorous vacuole and continuing replication of intravacuolar amastigotes; (7) rupture

of heavily parasitized macrophage and release of

amastigotes; (8) phagocytosis of released amastigotes by a macrophage.

Sandfly stage: (9) ingestion of parasitized macrophages by sandflies after a blood meal taken from infected

humans or reservoir animals; (10) rupture of the ingested macrophages and release of amastigotes in the gutof sandflies; (11) replication of amastigotes and their differentiation into promastigotes; (12) replication of

promastigotes in midgut and insertion of their flagella into microvilli of the gut epithelial cells; (13) replication

of L. brasiliensis group in the pylorus and ileum of the sandfly hindgut as paramastigotes with broadenedflagella attached to the chitinous gut wall via hemi-desmosomes; (14) forward movement of promastigotes to

thoracic midgut as haptomonads with broad flagella attached to the chitinous gut wall; (15) sessile

paramastigotes with broad flagella attached to the chitinous wall of stomadeal valve, pharynx and buccal cavityor cibarium; (16) actively motile and infective promastigotes found in the proboscis, or mouth part, of

sandflies.



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Life Cycle of LeishmaniaThe bloodmeal of a few microlitres in volume accumulates in the abdominal

midgut of the sandfly and the digestive process is initiated. The bloodmeal is

enclosed in a peritrophic matrix, a lattice-like network composed of chitin fibrilsand glycoproteins, which is secreted by the gut epithelial cells. These alsosecrete digestive enzymes to enable breakdown of the bloodmeal nutrients, of

which haemoglobin is a major component. Amastigotes are liberated from theirdegrading macrophage host cells and become extracellular within the bloodmeal.They rapidly differentiate into promastigote forms by elongation of their cellbody and extension of the flagellum, and begin to multiply within the bloodmeal.

Like their amastigote counterparts, the promastigotes are well adapted tosurvive in this hydrolytic environment and can withstand exposure to the sandflydigestive enzymes. The promastigotes grow, divide and increase in numbers,

initially within the confines of the bloodmeal contained in the peritrophic matrix.After 34 days the peritrophic matrix begins to break down, assisted by theaction of a parasite secretory chitinase. This enables the promastigotes to

escape the abdominal midgut and become fully established in the vector. Those

in the subgenus Leishmania do so by spreading forward, attaching to themicrovillar border of the midgut epithelium, to the cuticular surface of the

stomodeal valve and foregut, and by embedding themselves in a gel-like matrixof parasite origin in the anterior midgut. Those in the subgenus Viannia do so bymigrating backwards into the hindgut and attaching to the cuticular surface

found there. They multiply at this site for a period and then migrate forward tothe anterior midgut. Eventually, in both subgenera, promastigotes are found inlarge numbers in the anterior midgut and foregut 1 2 weeks after the initialbloodmeal. From this position they can be transmitted when the sandfly takes

her next bloodmeal.Transmission is effected by a specific life-cycle stage, the metacyclic

promastigote. During their multiplication and migration in the sandfly gut, thepromastigotes undergo various morphological and biochemical changes.Metacyclic promastigotes are produced towards the end of the developmentalsequence and possess properties that preadapt them for survival in a

mammalian host. They are biochemically intermediate between otherpromastigotes and amastigotes, expressing some genes in common with

promastigotes, others in common with amastigotes, as well as metacyclic-specific genes. They are also highly infectious to a suitable mammalian host incomparison with other promastigote forms, as a result of their ability to avoidcomplement-mediated lysis and to stimulate their own uptake by macrophages.

Metacyclic promastigotes are dedicated to transmission and represent asignificant proportion of the total promastigote population in a mature infection.

When the infected sandfly probes and feeds on a new mammalian host,metacyclic promastigotes are inoculated into the wound via the proboscis.Interestingly, infected sandflies experience more difficulty in engorging andprobe more frequently than uninfected flies, which enhance parasite

transmission. This appears to be due to the solid mass of parasites embedded intheir gel-like matrix in the anterior midgut. Once deposited in the skin,metacyclic promastigotes are engulfed by macrophages, differentiate into

amastigote forms, and take up their intracellular residence.


life cycle of leishmania sp

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