Open access peer-reviewed chapter

Leishmaniasis: Molecular Aspects of Parasite Dimorphic Forms Life Cycle

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Natanael Endrew Souto Maior Torres Bonfim, Ana Lígia Barbour Scott and Leonardo de Azevedo Calderon

Submitted: 11 November 2021 Reviewed: 23 December 2021 Published: 14 February 2022

DOI: 10.5772/intechopen.102370

From the Edited Volume

Leishmaniasis - General Aspects of a Stigmatized Disease

Edited by Leonardo de Azevedo Calderonon

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According to WHO, Leishmaniasis is a complex neglected disease caused by a protozoa parasite from over 20 Leishmania species transmitted by more than 90 sandfly species, showing three main forms: visceral, cutaneous, and mucocutaneous. The efficient prevention and control of leishmaniasis are very difficult to achieve, depending on the combination of different intervention strategies, usually resulting in failure. Additionally, the correct diagnostics require the combination of clinical signs with laboratory tests, and only a few therapeutical options are available for patients. To improve this scenario, greater efforts in research for control and treatment are needed. For this purpose, the study and understanding of the life cycle of Leishmania are mandatory for all researchers who intend to dedicate their careers to the different aspects of this important disease. In order to support beginning researchers in the study of leishmaniasis, we propose in this review an update in the current knowledge about the major molecular aspects involved in the development of dimorphic forms of Leishmania parasites that replicate in the gut of sandflies (promastigotes) and in mammalian cells (amastigotes) and the relationship with host’s immune system.


  • neglected disease
  • protozoan
  • leishmania
  • amastigote
  • promastigote

1. Introduction

The vectors of leishmaniasis are dipterans belonging to the Psychodidae family, belonging to the genera Phlebotomus (Old World), and Lutzomyia (New World), with wide distribution in warm and temperate climates [1]. Only female sandflies are hematophagous and when infected become vectors [2], they can contaminate, in addition to humans, other mammals such as domestic dogs and cats, making them important reservoirs of the protozoan [3]. These vectors have been more active in the twilight and post-dusk, sheltering during the day in humid, shaded places and well protected from the winds, for example, wild animal burrows, wood holes, bamboo cavities [4].

Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious species of Leishmania and weakness of the host [5]. Leishmaniasis presents an unstable epidemiological pattern, presenting unpredictable fluctuations in the number of cases in each region. In the Old World, it was initially described as a dermal condition known as Rish-e-Balkhi (Balkh Wound) as well as “kala-azar”. In the New World, leishmaniasis parasites were first described in 1909 by Adolpho Carlos Lindenberg, Antonio Carini, and Ulysses de Freitas Paranhos in skin lesions of patients with ‘Bauru’s ulcers’ in the state of São Paulo, Brazil [6]. Currently, there are three groups of parasites of the genus Leishmania classified into different subgenera and these vary depending on which parts of the vector’s gut are colonized by the parasites [7].

It is now known that leishmaniasis can present different characteristics that vary from skin lesions (such as erythematous or hypopigmented macules, papules, nodules, and patches) to visceralization, depending on the species of infecting parasite and the immune response developed by the host (Figure 1). However, it is known that cultural, environmental, and socioeconomic factors play an important role. Furthermore, due to the outbreak of tegumentary leishmaniasis in conflict zones in the Middle East, it reveals that war, ecological disasters, and forced migration are other factors associated with leishmaniasis risk factors [6]. Leishmaniasis-causing protozoa have two main life cycle morphologies: the amastigote phase [without apparent flagellum], which is intracellular in the mammalian host, and the promastigote phase [presence of flagellum in the anterior position of the cell] in the fly. The promastigote phase presents five main forms: procyclic, nectomonad, leptomonad, haptomonad, and metacyclic [7]. The growth of the flagellum in the promastigote occurs in several cell cycles. There are clear implications for the mechanisms of regulation of flagellum length, life cycle stage differentiation, and trypanosomatid division in general, and post-genomic analyzes of Leishmania cell biology have contributed to a better understanding of these mechanisms, not only regarding cell differentiation but also to the molecular mechanisms behind the protozoan infection, both in the vector and in the hosts [8].

Figure 1.

Representative scheme of the genus Leishmania classification illustrating three subgenres. The species presented include some of the more investigated that are the focus of biomedical research. They were colored by occurrences in the old world (blue boxes) and new world (red boxes), and the without colors occur in both regions. Parasites of the Leishmania and Viannia subgenus infect mammals, while Sauroleishmania infects reptiles as vertebrate hosts. Adapted from [1, 7].

Studies indicate that leishmaniasis parasites have adaptation mechanisms that allow the optimal activity of each life stage at its corresponding environmental pH [9]. For example, at pH 7.0 it produces morphologically mixed populations of promastigotes in the stationary phase, but it also includes a subpopulation with similar morphology to the metacyclic (Figure 2) [18, 19].

Figure 2.

Representative scheme of Leishmania differentiation process inside the sand fly vector. AM = amastigote form, the decrease in temperature and an increase in pH is detected by the cell and stimulate cell differentiation [10, 11], through modulation of the expression of genes linked to cell functions [12]. PP = pro-cyclic promastigote form, the secretion of chitinol enzymes aids in the escape from peritrophic membrane allowing the fixation on the vector intestine wall [13], the decrease in pH linked to the increase in glucose in the medium stimulates differentiation and migration according to the gradient of glucose concentration [14] by modulating the expression of genes linked to different cellular functions [12]. NP = Nectomonad Promatigote form, migrate to the thoracic portion of the midgut and begin to secrete PSG [15], as well as a decrease in the expression of several genes [12]. LP = Leptomonad Promatigote form, PSG secretion and detection of decreased oxygenation and pH actives signals for cell differentiation [16] into HP = Haptomonad Promatigote which attaches to the thoracic midgut wall and produces the PSG gel [17], or differentiates into MP = Metacyclic Promatigote form, the infecting phase, which migrates to the anterior portion of the sand fly intestine and infects the host during the next meal [14]. The increase is represented as blue arrows and the decrease is represented as red arrows.


2. Amastigote form

Amastigote means “without apparent flagellum”. The flagellum in amastigotes is internal and non-functional [7, 20]. This phase is a response to the phagocytation by its host’s defense cells, presenting itself in an intracellular form inside the phagolysosome [21].

After the blood-feeding, digestive enzymes, including trypsin, chymotrypsin, aminopeptidase, carboxypeptidase, and alpha-glycosidase degrade ingested infected cells and expose amastigote forms to the peritrophic membrane. The change in conditions from the mammalian host to the vector’s gut, active membrane receptors that detect the change in the environment as the pH increases, from ~4.0 to 5.5 in the phagolysosome to ~6.8 to 7.4 in the midgut vector [14, 21, 22] and temperature decrease, stimulate the development of the parasite into promastigote form [10, 11].

An important response of the parasite to this environmental change is the modulation of enzyme activity in the midgut, assigning different roles to these molecules than that suggested for the mucin-like structures, which appear to protect the parasite surface against the proteolytic enzymes [14]. The secretion of chitinase and N-acetylglucosaminidase enzymes protects from the intense enzymatic activity resulting from digestion, allowing the escape of peritrophic membrane towards the intestinal wall of the vector [13].

Several intracellular signals are triggered and are directly related to the transition from amastigote to promastigote. Relative expression studies revealed increased expression of several genes related to: (calmodulin binding; Cyclic nucleotide biosynthetic process; GTPase activity; GTP binding; DNA association; Nucleosome activity; Nucleosome assembly; Synthesis-coupled proton transport ATP; Mitochondrial proton transporter ATP synthase; Intracellular signal transduction; Dinein complex; Protein complex; Protein heterodimerization activity; Protein polymerization; Proteolysis; Phosphorus-oxygen lyase activity; Calcium-dependent cysteine-type endopeptidase] and a decrease in the expression of genes related to: (Antioxidant activity; Peroxiredoxin activity; Cysteine-type peptidase activity; DNA catabolic process; Triglyceride lipase activity) [12].

Transformation of amastigotes to promastigotes occurs within 12–18 h. These initially transformed promastigotes are termed procyclic and remain short, ovoid, and only slightly mobile [14].


3. Promastigote forms

3.1 Procyclic form

A procyclic promastigote is similar to a cell in G1 or post-S phase that has inherited the new short flagellum [23]. Its morphological characteristic is a body length of 6.5–11.5 μm and the flagellum is shorter than the body length and can have variable body width [20]. The intense multiplication of these forms starts at approximately 18–24 h [14], the divisor promastigotes are found in rosettes with flagella directed towards the center. In promastigotes, the flagellum extends from the cell body, hits and moves the organism, emerging from the anterior end of the cell [7].

Membrane protein classes of the parasite enable the attachment of the procyclic promastigote to the midgut wall of the vector and compatibility between Leishmania species with the vector species. The main membrane glycoconjugates, including their unique and common structures, are lipophosphoglycans–LPG, glycophosphatidylinositol lipids–GIPLs, glycoprotein 63–gp63, secreted acid phosphatases–sAP, secreted proteophosphoglycans–sPPG [14].

The fact that significant differences in LPG-mediated binding were observed when different vector species were compared suggest that the molecules that serve as parasite attachment sites can vary between different species of sandflies.

Serum digestion products destroy incompatible Leishmania species, furthermore, studies suggest that inter- and intraspecies-specific polymorphisms in the LPG phosphoglycan domains may result in species- and strain-restricted intestinal binding and thus determine vector competence. Species- and strain-specific and may therefore provide the evolutionary pressure for structural LPG polymorphisms [14, 24]. Developmental-regulated modifications in LPG structure control the specificity of the midgut adhesion stage [25, 26]. Recent findings indicate that non-LPG-mediated fixation is used by some other species of Leishmania [27, 28, 29, 30, 31].

The gp63, also known as leishmanolysin, is a 63 kDa zinc metalloproteinase containing a GPI anchor and is expressed on the surface of promastigotes of several Leishmania species. It plays an important role in the annexation of the leishmaniasis protozoan and has stood out in several studies related to the understanding of the development and virulence of the parasite [31, 32, 33, 34, 35, 36].

Gut-associated lectins or lectin-like molecules, which have been described for sandflies and presented as signaling sites conducive to parasite fixation [37, 38, 39].

Alternatively, lower affinity and less specific interactions, mediated by shared covering structures and/or flagellar proteins, may be sufficient for the parasite to resist the expulsive force it is exposed to in the vectors. Directing the anterior migration of unattached promastigotes to the thoracic midgut and stomodeal valve has generally been attributed to a glucose concentration gradient [14].

3.2 Nectomonad form

During 36–60 h, rapid multiplication continues, accompanied by the transformation of promastigotes into a long, slender, highly mobile form called nectomonads [14]. Nektós, comes from the Greek and means: “who swims”. Its morphological characteristic is the body length greater than or equal to 12 μm with variable body width and flagellar length [20]. A nectomonad promastigote is like an S-phase cell [23]. The cell differentiation signals triggered, in comparison to the procyclic ones, a significant decrease in the expression of genes related to: Nucleosome activity and assembly; protein heterodimerization; DNA association; core; kinetochore; administration of calmodulin [12].

3.3 Leptomonad form

By 60–72 h, an enormous number of nectomonads are found bundled up in the anterior portion of the abdominal midgut, with many attached via their flagella to the microvilli of the epithelial cells. The anterior migration of promastigotes to the region of the cardia [middle thoracic intestine] and stomodeal valve proceeds until a large accumulation of parasites behind the valve is reached. A leptomonad promastigote is similar to a cell in the same stages of the cell cycle as a procyclic promastigote, but which has inherited the older, longer flagellum [23]. Leptos, comes from the Greek and means: “slender, thin, small”. Its morphological characteristic is body length 6.5–11.5 μm, with flagellum greater than body length and variable body width [20]. Found lining the surface of the stomodeal valve and there can be differentiated haptomonad and metacyclic promastigotes [40].

3.4 Haptomonad form

It is the transformation of leptomonads into short, broad forms called haptomonads, which are occasionally seen to divide [7]. It comes from the Greek haptein, and means: “to hold, denoting contact or combination”, the morphological characteristic of haptomonads is the discoid expansion of the tip of the flagellum, with body shape and variable flagellar length [20]. The haptomonad forms bind through hemidesmosomes to the thin cuticular layer called the intima of the stomodeal valve or to each other through the secretion of a viscous gel-like matrix that restricts its motility [17].

The main component of the gel secreted by promastigotes (PSG) is a high molecular weight glycoprotein called filamentous proteophosphoglycan [15]. The identification of PSG strengthened the hypothesis of vector valve blockage, because the gel-forming properties of the filamentous proteophosphoglycan–fPPG may provide the physical obstruction necessary to cause regurgitation in the vector during repast [7].

The gelatinous nature of PSG, together with its high cell density, can cause local oxygen depletion, and anaerobiosis is also known to stimulate metacyclogenesis [16]. Furthermore, after differentiating leptomonad promastigotes in the middle of the PSG plug, metacyclic promastigotes can migrate to either pole, concentrating on the former in response to a chemotactic suggestion. The possibility of Leishmania responding to sugars or saliva released from the culture that could form a gradient in the midgut remains to be addressed [20].

3.5 Metacyclic form

The name “metacyclic” comes from the Greek Meta and means: “Between”. They are morphologically classified as short, slender, body length less than or equal to 8 μm, body width less than or equal to 1 μm, and highly active with a flagellum at least twice the length of the cell body and are generally not seen in the division [7, 20].

When compared with the gene expression in the form of neptomonads, we can observe the regulation of several cellular activities, with the negative expression of genes related to rRNA processing and the small subunit process (SSU) [12].

Metacyclic promastigotes, originating from the foregut or behind the stomodeal valve to the esophagus, pharynx, and proboscis, are inoculated during the meal, where they initiate the infection in the mammalian host [14]. However, there are at least three known components that lead to infection by the leishmaniasis protozoa: the metacyclic promastigotes themselves, which are obviously essential for transmission; sand fly saliva; and the gel secreted by promastigotes–PSG. Sandfly saliva is a well-established disease exacerbation factor [41], at least for tegumentary leishmaniasis. This is due to the fact that it contains potent compounds with vasodilatory and anti-hemostatic properties [42]. Co-inoculation of saliva with parasites has been shown to worsen the disease in several studies, and this is due to the modulatory capacity of the immune response to contribute to parasite survival and replication [43, 44, 45]. Likewise, PSG has also been shown to contribute to the worsening of the disease, being directly related to the increase in the number of metacyclic promastigote parasites co-inoculated with saliva [27]. The presence of parasites in the salivary glands of sandflies has already been reported by some studies and, therefore, it has been proposed as a fact of great relevance for transmission [46, 47].


4. Molecular aspects of the infection

The first interactions between Leishmania and the host’s immune response are closely linked to the evolution of the disease or protection against the protozoan, and the vector’s saliva directly contributes to these interactions [48]. Sandfly saliva is composed of active molecules that cause an imbalance in homeostasis at the host site, and aid repast [49]. The saliva of these arthropods contains a vast repertoire of pharmacologically active molecules that hinder the host’s hemostatic, inflammatory, and immunological responses [48, 49]. When sand fly saliva is injected into the host’s skin, it induces infiltration of inflammatory cells [50] and antibody production [51, 52, 53]. These disturbances in tissue physiology may also favor the release of Leishmania parasites, as the key to the success of Leishmania parasitism is the ability to evade host immune responses [48]. In this setting, immune complexes are formed [53] in the early stages of exposure. In addition, sand fly saliva also modulates costimulatory molecules and cytokine release by antigen-presenting cells [54, 55, 56].

Several active compounds with pharmaceutical properties have already been isolated from the saliva of sand flies such as the anticoagulant compound of Lufaxine (Inhibitor of Factor Xa from Lutzomyia longipalpis). This recombinant protein has potent and specific anticoagulant activity against factor Xa, a serine protease that cleaves prothrombin to generate thrombin and is involved in both the extrinsic and intrinsic coagulation pathway [57], preventing the activation of receptor 2 activated by protease and thereby inhibiting inflammation and thrombosis in C57BL/6 mice [58].

The action of the LuloHya compound, which acts as a hyaluronidase [55], has also been reported, and when co-inoculated with the parasites provides a more successful infection by Leishmania [59, 60, 61]. The Lundep protein, on the other hand, acts as an endonuclease and helps in the survival of parasites by inhibiting neutrophil traps (NET) in addition to preventing the activation by contact of FXIIa in human plasma [56, 60].

One of the most studied salivary peptides is a potent vasodilator known as maxadilan (MAX). In addition to vasodilation, this compound can also act as an immunomodulator in the host. It can up-regulate cytokines associated with a type 2 response (IL-10, IL-6, and TGF-β) and down-regulate type 1 cytokines (IL-12p70 and TNF-α), NO, and CCR7. This increased parasite survival in the vertebrate host in the early stages of infection [55, 56]. Studies involving the inhibition of human complement by the saliva of the sand fly Lutzomyia longipalpis showed the existence of inhibitors of the classical pathway in this species. As the anti-complement compound Salo [62] and is also considered as a potential transmission-blocking vaccine candidate against leishmaniasis [63].

Pharmacologically active molecules such as Maxadilan in L. longipalpis or PP-1 PP-2A inhibitors [Protein phosphorylation and dephosphorylation reactions, mediated by protein kinases and PPs, respectively, trigger signal transduction events that control diverse cellular responses to internal and external signals [64, 65] present in the saliva of P. papatasi, probably evolved to facilitate blood-feeding. However, as with many other biomolecules, salivary factors also exhibit other activities. In this case, Leishmania parasites benefit from the immunomodulatory effects of certain salivary factors to facilitate their establishment in the hostile environment of vertebrate skin [66].

Taken together, these data indicate that saliva is an endless issue, and several factors remain to be defined and how blocking these molecules is an open field for alternative tools against transmission [48, 49, 67]. Figure 3 briefly illustrates the main aspects of how the infection of leishmaniasis parasites occurs in the host.

Figure 3.

Schematic representation of the leishmaniasis stages of infection. Parasite infection: Leishmania sp. enters through the lesion caused by the proboscis during the meal and infect local macrophages. Stimulated by compounds with vasodilating and anti-hemostatic properties present in the vector’s saliva, an inflammatory reaction begins in the region where more immune cells are recruited to the site and can also be infected by protozoa in metacyclic form. Once phagocytosed, the protozoa become different in the amastigote form in the phagosome. Growth and survival of Leishmania sp.: Infected macrophages secrete anti-inflammatory and pro-inflammatory mediators, initiate immune response mechanisms, neutrophils release cytokines and reactive oxygen species–ROS in the region and monocytes, which differ into macrophages and dendritic cells, which become infected and migrate to other tissues. The increase is represented as blue arrows and decrease is represented as red arrows.

Recognition of the parasite by the host’s immune system cells is the key to triggering effective Leishmania-specific immunity [5]. However, the parasite can persist in the host’s myeloid cells, evading, delaying, and manipulating the host’s immunity to escape host resistance and ensure its transmission [5].

Neutrophils are the first to infiltrate infection sites, where they generate an inflammatory response that restricts the parasite and acts to protect the organism, fighting infection through a series of mechanisms, being considered important modulators of leishmaniasis [68]. They are responsible for the formation of web-like structures called neutrophil extracellular traps (NETs) that can capture and/or kill microorganisms [68]. However, for some species of Leishmania, neutrophils can act as carriers that facilitate the silent infection of macrophages [69, 70, 71]. The ‘Trojan Horse’ model is based on the silent transmission of the parasite from neutrophils to macrophages and dendritic cells when macrophages and cells phagocyte from apoptotic neutrophils that are contaminated by Leishmania [70]. This model is evidenced in the reported ability of some Leishmania species, such as L. major and L. braziliensis [72, 73], to induce neutrophil apoptosis.

Macrophages are the main effector population involved in parasite elimination [5]. However, macrophages are the main host cells where the parasites grow and divide. The parasites infect, multiply gradually, and finally destroy macrophages releasing large numbers of viable amastigotes in the region [74]. Once inside the macrophage, and depending on the Leishmania species, the parasites delay the formation and maturation of phagosomes, preventing phagosome acidification and the action of proteases, while guaranteeing the nutrients necessary for its survival. Furthermore, the parasites modulate the cytokine secretion pattern and inhibit the generation of NO and ROS, while extending the survival of infected macrophages [5]. Genomic and transcriptomic analyzes have largely contributed to the understanding of the biology of Leishmania and revealed to us about the complex interactions that occur within the parasite–host-vector triangle, these interactions are responsible for the rapid activation and deactivation of various signaling pathways that lead to functions of macrophages [e.g., phagocytosis, chemokine secretion, and prostaglandin secretion] [75, 76]. Extracellular matrix interactions, metabolic changes, modulation of gene expression and several mechanisms that are still being studied have revealed how cell–cell interaction occurs and why leishmaniasis is such a complex disease as shown in Figure 4. The elimination of parasites by macrophages requires the preparation and development of an adaptive effector Th1 immunity driven by specific subtypes of dendritic cells [5].

Figure 4.

Diagram representing the major reports about modulation of internal reactions in macrophages infected by the parasite causing leishmaniasis. Leishmania sp. internalization and cell differentiation is successfully achieved, mediated by modulating the expression of genes linked to various cellular functions [12] and by the alteration of signaling events in the host cell, leading to increased production of autoinhibitory molecules such as TGF-beta and decreased induction of cytokines such as IL12 for protective immunity. The production of nitric oxide is also inhibited. furthermore, defective expression of major histocompatibility complex (MHC) genes silences subsequent macrophage-mediated T cell activation, resulting in abnormal immune responses [77]. SHP-1 down-regulates JAK2, Erk1/Erk2 MAP, NF-B, IRF-1, and AP-1 kinases, thereby inhibiting IFN-inducible macrophage functions (e.g., nitric oxide, IL-12 production, and immunoproteasome formation), STAT1 degradation by the proteasome is dependent on PKC and other phosphatases (eg, phosphatase IP3 and calcineurin) and surface parasite molecules such as LPGs play a key role in altering several secondary pathways, for example, PKC, Ca+2 and phosphatidyl inositol), regulating important phagocyte functions such as NO and superoxide production [75]. The increase is represented as blue arrows and the decrease is represented as red arrows.

Studies analyzing neutrophils infected by L. major parasites have shown that, when phagocytosed by cells in the skin tissue, they have the ability to inhibit the maturation and migration of dendritic cells, resulting in a delay in the development of adaptive immunity [72, 78, 79]. Dendritic cells are essential for the generation of a Th1-mediated immune response, fundamental for the control of leishmaniasis [80, 81, 82]. These parasites can act at different levels to inhibit dendritic cells, including modulation of the MAPK pathway, decreased antigen presentation capacity and IL-12 secretion, this inhibition being mediated by the activation of protein tyrosine phosphatase (PTPs) [83, 84]. In summary, the internalization of the opsonized protozoan by dendritic cells via FcγR (Fcγ receptor) promotes dendritic cell activation and IL-12 production. Furthermore, there is a down-regulation of costimulatory molecules, CD40 and CD86 after infection and gp63 cleaves the SNAREs protein (soluble NSF binding protein receptor), preventing the assembly of the NADPH oxidase complex [5]. An analysis of the gene expression of lesions with Cutaneous Leishmaniasis showed increased P27 [85] and decreased expression of the A2 gene [86]. IL-10 is important for the persistence of the parasite in the lesion, preventing its complete elimination from the lesion, despite the presence of a protective immune response [87]. Furthermore, circulating antibody is crucial for susceptibility to the development of tegumentary leishmaniasis [88] and a progressive increase in tissue IL-10 expression during infection suggests a role in susceptibility [89]. The amastigotes from the cutaneous leishmaniasis lesion are coated with IgG, and the internalization of opsonized amastigotes by macrophages induces the production of IL-10 and a consequent increase in the intracellular growth of the parasite [90].

Tissue damage is promoted by inappropriate epidermal signals driven by dendritic cells. Furthermore, studies indicate that nTregs are essential for the development and maintenance of persistent skin infection and reactivation of infections caused by the Leishmania parasite [91]. Understanding which dendritic cell populations are critical to triggering and achieving immunity to Leishmania and how parasites inhibit its activation and migration will help to improve a rational design of vaccines aimed at neutralizing the parasite’s virulence factors, along with the use of the most appropriate adjuvants [5]. These recurrent injuries may result from the Koebner phenomenon [92] which refers to skin lesions appearing in lines of mechanical trauma, seen in some skin diseases such as psoriasis.

Antimicrobial peptides are innate immunity mechanisms that contribute to host defense. LL-37 is a peptide derived from human cathelicidin (CAP180, a multifunctional regulator of the innate and adaptive immune response, having a leishmanicidal activity, increasing phagocytosis in dendritic cells and macrophages, and acting as an activator or suppressor of the adaptive immune response depending on the concentration [91].

Natural regulatory T cells rapidly accumulate in the dermis, where they suppress, both through IL-10 dependent and independent mechanisms, the capacity of CD4 + CD25 effector T cells to eliminate the parasite from the site [91]. One of the immunopathological consequences of active visceral leishmaniasis in humans is the suppression of T cell responses mainly to the Leishmania antigen [93]. The immune responses induced during visceral leishmaniasis in experimental data are markedly different from those induced in cutaneous leishmaniasis [94]. Furthermore, gene expression studies of tissues infected with visceral leishmaniasis reveal the modulation of the expression of genes P27, Ufm1 [85] and A2 [95]. A spectrum of clinical manifestations occurs in visceral leishmaniasis, ranging from asymptomatic or oligosymptomatic disease to progressive disease with severe manifestations such as hepatosplenomegaly, fever, pancytopenia, and hypergammaglobulinemia [96].

These particularities must have to be studied in order to permit the understanding of how different Leishmania species could promote different forms of the disease can generate such different immune responses [94].


5. Conclusion

The morphological development of the parasite has been regulated by the environment in which it is found, being perceived by chemotactic receptors that identify these environmental changes (e.g. pH and oxygenation), modulating several genes and thus triggering various intracellular processes, processes that depend on the stage of development that the parasite is at when receiving such stimuli. About the molecular aspects involved in the infection, we can say that current research has indicated a strong relationship between the immune response and the way in which leishmaniasis will manifest itself.

In order to benefit the socio-economically vulnerable individuals affected by leishmaniasis, many young researchers start their studies in leishmaniasis from an early age in scientific initiation programs, often conducting their studies well beyond the PhD. These young researchers are the audience that this book chapter is dedicated. Because we believe that the study and understanding of the life cycle of Leishmania are mandatory for all researchers who intend to dedicate their careers to the different aspects of this important disease. From epidemiological studies to the development of new therapies, a good understanding of the parasite’s life cycle is essential for the success of all initiatives.


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Written By

Natanael Endrew Souto Maior Torres Bonfim, Ana Lígia Barbour Scott and Leonardo de Azevedo Calderon

Submitted: 11 November 2021 Reviewed: 23 December 2021 Published: 14 February 2022