Leishmania infection

Describe the roles of the innate and adaptive immune system during Leishmania infection


Leishmania is a protozoan parasite which belongs to the order Kinetoplastida, the family Trypanosomtidae, and the genus Leishmania. It causes an infectious disease called Leishmaniasis. The parasite can be transmitted from infected animals to humans or human-to-human via the bite of female sand flies of the genus Phlebotomus. Leishmania species exist exclusively within mononuclear phagocytes as a flagellated intracellular amastigote in vertebrates. However, the parasite resides as flagellated extracellular promastigotes in the intestine of the sand fly vector. At present, about 12 million people are infected on a global scale. In addition, about 2 million new cases are described each year. Leishmaniasis has spread to 88 countries, which include 72 developing and 16 developed nations. Several studies have described many types of the disease, but it is mainly two forms that infect people. The first type is called cutaneous leishmaniasis disease (skin ulcers) caused by L. major and causes 1.5 million new cases annually. The second type is visceral leishmaniasis disease caused by L. donovani; 500,000 cases appear yearly. More than 20 genotypes and subspecies of Leishmaniasis can infect people; therefore, each species causes a variety of signs and symptoms (Karunaweera, 2009; Kima, 2007).

A number of researchers have studied the immunology of human disease in several endemic areas. The results show that the protection of leishmanial infection is controlled by cell-mediated immune responses. In addition, the majority of information on the types of infections, the chemotherapy and the immunological mechanisms that have been described for protective immunity versus leishmaniasis were collected from research on animal models such as mice (Stebut et al., 2004). This essay will describe the types of immune response that are induced by Leishmania during infection of the host.

The immune response to Leishmania:

Several investigators have demonstrated that leishmaniasis mainly depends upon the genotypes of the protozoan and the immune response of the host. The genotypes of parasites infecting the host can influence the immune response to Leishmania infections. Moreover, a single, particular species of Leishmania is able to cause more than one clinical syndrome and the severity of the disease changes from one patient to another (Dunnig, 2009).

In order to improve a successful parasitic connection with its host, the parasite has the ability to avoid both innate and adaptive immune responses, such as macrophages, dendritic cells (DC), natural killer (NK) cells, T helper cells (CD4+) and cytotoxic cells(CD8+), in which they can play an essential role in immune response to Leishmania infection. Macrophages are the main target for the Leishmania parasite. Therefore, the organs that include phagocytes and macrophages will be the most infected, such as the bone marrow, spleen and liver. When the sand fly bites the mammalian host, it injects its saliva with the promastigotes - in extracellular form - into the dermis of the host. These are engulfed by macrophages, in which there are amastigotes in intracellular form, which are thus resistant to proteolysis and degradation in the phagosome. The amastigotes remain inside the macrophages, where they reproduce quickly via binary fission until the cells burst. As a result, the amastigotes spread and infect other cells. It is an effective mechanism, which is used by the parasites to avoid the humoral branch of the immune system (Liese et al, 2008; Dunning, 2009).

A number of studies have demonstrated that Leishmania promastigotes have the ability to bind to the surface of macrophages through molecules like complement receptors Cb3, CR1and CR3 in order to start internalisation of amastigotes. Fc and complement receptors may lead to phagocytosis. Leismania promastigotes are shielded by a compact surface glycocalyx that is composed mainly of molecules bound by glycosylphosphatidylinositol (GPI). These GPI-anchored molecules contain proteins, such as the parasite surface protease gp63 and proteophsphogycans (PPGS). Moreover, the biggest component is comprised of the large GPI-anchored phosphoglycan called lipophosphoglycan (LPG). Both gp63 and LPG are responsible for the toxicity of the parasite. The glycoprotein gp63 plays an important role in the parasite's entry into and survival in the host cells. It is an endoproteinase, which has the ability to degrade lysosomal proteins, immunoglobulins and complement factors. It has a proteolytic activity at pH4, which plays a central role in the survival of amastigotes under the acidic condition of the macrophage phagolysosomes. In addition, LPG is required for its remaining alive inside the vector. It also plays an essential role in starting successful intracellular parasitism within the macrophage. Moreover, Toll-like receptors (TLRs) are another type of receptor molecule which has been discovered on the surface of the macrophages and dendritic cells. TLR signalling is important for immune responses against Leishmania infection. In addition, they have the ability to bind to Leishmania and can also manage the interactions between the host and parasite. For instance, TLR2 is contributed in NK cells' activation in animal models of visceral and cutaneous leishmaniasis, L. donovani and L. major, respectively, whereas TLR2 and TLR3 are necessary for the intracellular killing of L. donovani in (INF- γ) - primed MФs (Vargas-Inchaustegui et al.,2009; Awasthi et al., 2004; Kima, 2007).

Dendritic cells and Leishmania infection:

Recent findings indicate that the Leishmania amastigotes have been found within dendritic cells (DC), which may also be host cells for these parasites. Mature DCs are required to stimulate the activation and differentiation of naïve T lymphocytes by producing of (IL-12). As a result, if these cells are infected by the parasites, the onset of the adaptive immune responses will be delayed, because the maturation and migration of dendritic cells are important processes for activation of T naïve cells which will develop to either Th1 cells or Th2 cells (Antoine et al., 2004; Gibson-Corley et al., 2010).

The role of T immune responses cells and B cells with Leishmania infection:

Several studies have indicated that the resistance of intracellular parasite infections is regulated by T cells. These outcomes have come from research demonstrating that several strains of mice have shown different susceptibility to the disease. For example, BALB/c mice are highly susceptible to infection with Leishmania spp., while C57BL/6 mice are resistant to infection. Numerous studies have illustrated that C57BL/6 mice develop a Th1 immune response, which is responsible for secreting interleukin-2 (IL-2) and interferon-gamma (INF-γ). These cytokines have the ability to delay the process of parasite growth, allowing quick recovery from severe infection. This because INF- γ stimulates macrophages to induce enzyme-inducible nitric oxide synthase (iNOS2) which has the ability to encourage producing of nitric oxide (NO). The presence of this component, NO, leads to the destruction of intracellular amastigotes. Conversely, in BALB/c mice, improved Th2 immune cells induce early IL-4 and IL-10 after infection. Introducing these interleukins inhibits INF- γ and IL-2, the major cytokines that are required for ending Leishmania growth.

Furthermore, several studies have recommended that B cells and their Ig secretion play an important role in disease pathogenesis. It has been discovered that there are types of B cells - B1, B2 and B regulatory - which are able to produce cytokines IL-12/ INF- γ., IL-4 and IL-10 respectively. IL-10 production by Breg cells have the ability to promote the development of Th2 immune response and the capability of inhibiting pro-inflammatory cytokines such as INF- γ. There is another observation suggesting that cytokines other than IL-4 might contribute susceptibility to infection with L. major. However, several studies have illustrated the role of macrophages (MФs), dendritic cells (DCs) and CD4+T cells in Leishmania infection, whereas less attention has been given to understanding how B cells and their antibody production might affect the outcome of infection (Antoine et al., 2004; Ronet et al., 2010).


Leishmania are a considerable public health problem in tropical and subtropical countries, and pose a severe disease threat to humankind. Leishmaniasis is a zoonotic disease, and it can be transmitted to humans by female sand flies which feed on the blood of humans and animals. There are two main forms of Leishmaniasis: Visceral Leishmaniasis (VL) and cutaneous Leishmaniasis (CL). The protozoa live dimorphically in their hosts, existing as promastigote forms in the gut of the shadfly, whereas in the final, mammalian host, presents in amastigote forms. These forms of Leishmania can infect macrophages (MФs), natural killer (NK) and dendritic cells (DCs) through interactions between their molecules, found on the surface of the phagocytises cells, and molecules of Leishmania surface. The amastigotes' interactions with mammalian cells encourage the production of INF- γ and IL-2, which are essential in the host's defence against Leishmania. These components have been found in some strains of mice which are considered to be resistant types. Susceptible strains induce the Th2 interleukins IL-4 and IL-10, and consequently suffer progressive disease. It has been discovered that B cells have an important immunity processes against Lieshmaina infection. However, more investigation and understanding are required for the role of B cells and their secretions in Leishmania infection.


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