Leishmania
Leishmania donovani in bone marrow cell.
Scientific classification
Domain: Eukaryota (unranked) Excavata Phylum: Euglenozoa Class: Kinetoplastea Order: Trypanosomatida Genus: Leishmania
Species
L. aethiopica L. amazonensis L. arabica L. archibaldi (disputed species) L. aristedesi L. (Viannia) braziliensis L. chagasi (syn. L. infantum) L. (Viannia) colombiensis L. deanei L. donovani L. enriettii L. equatorensis L. forattinii L. garnhami L. gerbili L. (Viannia) guyanensis L. herreri L. hertigi L. infantum L. killicki L. (Viannia) lainsoni L. major L. mexicana L. (Viannia) naiffi L. (Viannia) panamensis L. (Viannia) peruviana L. (Viannia) pifanoi L. (Viannia) shawi L. tarentolae L. tropica L. turanica L. venezuelensis Image File history File links No higher resolution available. ... Scientific classification or biological classification is a method by which biologists group and categorize species of organisms. ... Kingdoms Animalia - Animals Fungi Plantae - Plants Chromalveolata Protista Alternative phylogeny Unikonta Opisthokonta Metazoa Choanozoa Eumycota Amoebozoa Bikonta Apusozoa Cabozoa Rhizaria Excavata Corticata Archaeplastida Chromalveolata Animals, plants, fungi, and protists are eukaryotes (IPA: ), organisms whose cells are organized into complex structures by internal membranes and a cytoskeleton. ... This article is about the protist group called excavates. ... Typical Classes Euglenoidea Kinetoplastea Diplonemea Postgaardea The Euglenozoa are a large group of flagellate protozoa. ... Orders Trypanosomatida Bodonida The kinetoplastids are a group of flagellate protozoa, including a number of parasites responsible for serious diseases in humans and other animals, as well as various forms found in soil and aquatic environments. ... Genera Blastocrithidia Crithidia Endotrypanum Herpetomonas Leishmania Leptomonas Phytomonas Trypanosoma Wallaceina Trypanosomes are a group of kinetoplastid protozoa distinguished by having only a single flagellum. ...

Leishmania is a genus of trypanosome protozoa, and is the parasite responsible for the disease leishmaniasis.^[1] It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects hyraxes, canids, rodents, and humans. Leishmania currently affects 12 million people in 88 countries. For other uses, see Genus (disambiguation). ... Genera Blastocrithidia Crithidia Endotrypanum Herpetomonas Leishmania Leptomonas Phytomonas Trypanosoma Wallaceina Trypanosomes are a group of kinetoplastid protozoa distinguished by having only a single flagellum. ... Wikisource has an original article from the 1911 Encyclopædia Britannica about: Protozoa Protozoa (in Greek proto = first and zoa = animals) are single-celled eukaryotes (organisms whose cells have nuclei) that commonly show characteristics usually associated with animals, most notably mobility and heterotrophy. ... A parasite is an organism that spends a significant portion of its life in or on the living tissue of a host organism and which causes harm to the host without immediately killing it. ... Sandfly biting a humans little finger Sandfly is a colloquial name for any species or genus of flying, biting, blood-sucking Dipteran encountered in sandy areas. ... Species Species Phlebotomus longicuspis Species Phlebotomus papatasi Species Phlebotomus sergenti Phlebotomus is a genus of flies or diptera in the family Phlebotomidae, which generally includes sand flies. In the past, they were considered to belong to the family Psychodidae. ... The Old World consists of those parts of Earth known to Europeans, Asians, and Africans before the voyages of Christopher Columbus; it includes Europe, Asia, and Africa (collectively known as Africa-Eurasia), plus surrounding islands. ... Species Species Lutzomyia amazonensis Species Lutzomyia aragaoi Species Lutzomyia cruzi Species Lutzomyia intermedia Species Lutzomyia longipalpis Species Lutzomyia migonei Species Lutzomyia whitmani Lutzomyia is a genus of flies, or diptera, that generally includes sand flies. In the New World, Lutzomyia sand flies are responsible for the transmission of leishmaniasis, an... Frontispiece of Peter Martyr dAnghieras De orbe novo (On the New World). Carte dAmérique, Guillaume Delisle, 1722. ... This article does not cite any references or sources. ... Genera Procavia Heterohyrax Dendrohyrax A hyrax (from Greek shrewmouse; Afrikaans: klipdassie) is any of four species of fairly small, thickset, herbivorous mammals in the order Hyracoidea. ... Genera Alopex Atelocynus Canis Cerdocyon Chrysocyon Cuon Dusicyon Fennecus Lycalopex Lycaon Nyctereutes Otocyon Pseudalopex Speothos Urocyon Vulpes Canidae is the family of carnivorous and omnivorous mammals commonly known as canines. ... Suborders Sciuromorpha Castorimorpha Myomorpha Anomaluromorpha Hystricomorpha Rodentia is an order of mammals also known as rodents. ... This article is about modern humans. ...

Origin

The origins of Leishmania are unclear.^[2][3] One possible theory proposes an African origin, with migration to the Americas. Another migration from the Americas to the Old World about 15 million years ago, across the Bering Strait land bridge. Another proposes a palearctic origin.^[4] Such migrations would entail migration of vector and reservoir or successive adaptations along the way. A more recent migration is that of L. infantum from Mediterranean countries to Latin America (there named L. chagasi), since European colonization of the New World, where the parasites picked up its current New World vectors in their respective ecologies. This is the cause of the epidemics now evident. One recent New World epidemic concerns foxhounds in the USA. The Old World consists of those parts of Earth known to Europeans, Asians, and Africans before the voyages of Christopher Columbus; it includes Europe, Asia, and Africa (collectively known as Africa-Eurasia), plus surrounding islands. ... Satellite photo of the Bering Strait Photo across the Bering Strait Nautical chart of the Bering Strait The Bering Strait (Russian: ) is a sea strait between Cape Dezhnev, Russia, the easternmost point (169°43 W) of the Asian continent and Cape Prince of Wales, Alaska, the westernmost point (168°05... The Palearctic or Palaearctic is one of the eight ecozones dividing the Earth surface (see map). ... Latin America consists of the countries of South America and some of North America (including Central America and some the islands of the Caribbean) whose inhabitants mostly speak Romance languages, although Native American languages are also spoken. ... Frontispiece of Peter Martyr dAnghieras De orbe novo (On the New World). Carte dAmérique, Guillaume Delisle, 1722. ... In epidemiology, a vector is an organism that does not cause disease itself but which spreads infection by conveying pathogens from one host to another. ...

Pathophysiology

Leishmania cells have two morphological forms: promastigote (with an anterior flagellum)^[5] in the insect host, and amastigote (without flagella) in the vertebrate host. Infections are regarded as cutaneous, mucocutaneous, or visceral. The term morphology in biology refers to the outward appearance (shape, structure, colour, pattern) of an organism or taxon and its component parts. ... // A flagellum (plural: flagella) is a long, slender projection from the cell body, composed of microtubules and surrounded by the plasma membrane. ...

Cutaneous (localized and diffuse) infections appear as obvious skin reactions. The most common is the Oriental Sore (caused by Old World species L. major, L. tropica, and L. aethiopica). In the New World, the most common culprits are L. mexicana and L. (Viannia) braziliensis. Cutaneous infections are most common in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria. Mucocutaneous (espundia) infections will start off as a reaction at the bite, and can go via metastasis into the mucous membrane and become fatal. Mucocutaneous infections are most common in Bolivia, Brazil and Peru. Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ...

Visceral infections are often recognized by fever, swelling of the liver and spleen, and anemia. They are known by many local names, of which the most common is probably Kala azar,^[6][7] and are caused exclusively by species of the L. donovani complex (L. donovani, L. infantum syn. L. chagasi).^[1] Found in tropical and subtropical areas of all continents except Australia, visceral infections are most common in Bangladesh, Brazil, India, Nepal and Sudan.^[1] This article discusses the medical condition. ...

Treatment

Main article: Leishmaniasis

The treatment of this disease is sodium stibogluconate. Another solution which breaks down the lipophosphoglycan (LPG) is also a form of treatment being looked at. Those who feel they are infected should seek immediate attention. Transmission is mainly through the bite of sand flies but also through needle-sharing by drugs users. Most at risk are humans infected with HIV, canines and rodents. Sodium stibogluconate is a medicine used to treat leishmaniasis and is only available for administration by injection. ... Sandfly biting a humans little finger Sandfly is a colloquial name for any species or genus of flying, biting, blood-sucking Dipteran encountered in sandy areas. ... Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ...

Molecular biology

An important aspect of the Leishmania protozoan is its glycoconjugate layer of lipophosphoglycan (LPG). This is held together with a phosphoinositide membrane anchor, and has a tripartite structure consisting of a lipid domain, a neutral hexasaccharide, and a phosphrorylated galactose-mannose, with a termination in a neutral cap. Not only do these parasites develop post-phlebotomus digestion but, it is thought to be essential to oxidative bursts, thus allowing passage for infection. Characteristics of intracellular digestion include an endosome fusing with a lysosome, releasing acid hydrolases which degrade DNA, RNA, proteins and carbohydrates. Glycoconjugates is the general classification for carbohydrates covalently linked with other chemical species. ... Lipophosphonoglycan (or lipophosphoglycan) is a molecule found in Leishmania and other pathogens. ... In biology an endosome is a membrane-bound compartment inside cells. ... Organelles. ... In biochemistry, a hydrolase is an enzyme that can break a chemical bond by hydrolysis. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... Ribonucleic acid or RNA is a nucleic acid polymer consisting of nucleotide monomers that plays several important roles in the processes that translate genetic information from deoxyribonucleic acid (DNA) into protein products; RNA acts as a messenger between DNA and the protein synthesis complexes known as ribosomes, forms vital portions... Carbohydrates (literally hydrates of carbon) are chemical compounds that act as the primary biological means of storing or consuming energy, other forms being fat and protein. ...

Leishmania as component of CVBD

Canine Vector-borne Diseases (CVBD) covers diseases caused by pathogens transmitted by ectoparasites as ticks, fleas, sand flies or mosquitoes. CVBD is a term used internationally by veterinarians for Canine Vector-Borne Diseases -- in other words, diseases transferred to dogs by various parasitic vectors. ...

Other microorganism-based diseases caused by ectoparasites include Bartonella, Borrelia, Babesia, Dirofilaria, Ehrlichia, and Anaplasma. Bartonella is a genus of bacterium. ... Species Borrelia anserina Borrelia burgdorferi Borrelia is a genus of bacteria of the spirochete class. ... Species Babesia (syn. ...

Neutrophil granulocytes - the Trojan horses for Leishmania parasites

The strategy of the "Trojan horse" as a mechanism of pathogenicity of intracellular microorganisms is, to avoid the immune system and its memory function cleverly, with phagocytosis of infected and apoptotic neutrophils by macrophages, employing the non-danger surface signals of apoptotic cells. Pathogenicity is the ability of an organism to cause disease in another organism. ... In cell biology, molecular biology and related fields, the word intracellular means inside the cell. It is used in contrast to extracellular (outside the cell). ... A microorganism or microbe is an organism that is so small that it is microscopic (invisible to the naked eye). ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Steps of a macrophage ingesting a pathogen: a. ... A cell undergoing apoptosis. ... Neutrophil granulocytes (commonly referred to as neutrophils) are a class of white blood cells and are part of the immune system. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ...

Transmitted by the sandfly, the protozoan parasites of the genus Leishmania major may switch the strategy of the first immune defense from eating/inflammation/killing to eating/no inflammation/no killing of their host phagocyte' and corrupt it for their own benefit. They use the willingly phagocytosing polymorphonuclear neutrophil granulocytes (PMN) rigorously as a tricky hideout, where they proliferate unrecognized from the immune system and enter the long-lived macrophages to establish a “hidden” infection. Sandfly biting a humans little finger Sandfly is a colloquial name for any species or genus of flying, biting, blood-sucking Dipteran encountered in sandy areas. ... Protozoa (in Greek protos = first and zoon = animal) are single-celled creatures with nuclei that show some characteristics usually associated with animals, most notably mobility and heterotrophy. ... A parasite is an organism that lives in or on the living tissue of a host organism at the expense of it. ... Species (disputed species) (syn. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... A phagocyte is a cell that ingests and destroys foreign matter such as microorganisms or debris via a process known as phagocytosis. ... The word proliferation can refer to: Nuclear proliferation Chemical weapon proliferation the spread in use of other weapons systems Cell proliferation According to Gloria Anzaldúa (1990), the difference between appropriation and proliferation is that the first steals and harms; the second helps heal breaches of knowledge. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... An infection is the detrimental colonization of a host organism by a foreign species. ...

Uptake and survival

By a microbial infection PMN move out from the bloodstream and through the vessels’ endothelial layer, to the site of the infected tissue (dermal tissue after fly bite). They immediately start their business there as the first immune response and phagocyte the invader because of the foreign and activating surfaces. In that processes an inflammation emerges. Activated PMN secrete chemokines, IL-8 particularly, to attract further granulocytes and stimulate them to phagocytosis. Furthermore Leishmania major increases the secretion of IL-8 by PMN. In the parasites case, that may not sound reasonable at first. We can observe this mechanism on other obligate intracellular parasites, too. For microbes like these, there are several ways to survive inside cells. Surprisingly, the co-injection of apoptotic and viable pathogens causes by far a more fulminate course of disease than injection of only viable parasites. Exposing on the surface of dead parasites the anti-inflammatory signal phosphatidylserine, usually found on apoptotic cells, Leishmania major switches off the oxidative burst, so killing and degradation of the co-injected viable pathogen is not achieved. In case of Leishmania progeny is not generated in PMN, but in this way they can survive and persist untangled on the primary site of infection. The promastigote forms also release LCF (Leishmania chemotactic factor) to recruit actively neutrophils but not other leukocytes , for instance monocytes or NK cells. In addition to that, the production of interferon gamma (IFNγ)-inducible protein 10 (IP10) by PMN is blocked in attendance of Leishmania, what involves the shut down of inflammatory and protective immune response by NK and Th1 cell recruitment. The pathogens stay viable during phagocytosis since their primary hosts, the PMN, expose apoptotic cell associated molecular pattern (ACAMP) signaling “no pathogen”. A microorganism or microbe is an organism that is so small that it is microscopic (invisible to the naked eye). ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ... Interleukin-8 (IL-8) is a chemokine produced by macrophages and other cell types such as epithelial cells. ... Granulocytes are a category of white blood cells, characterised by the fact that all types have differently staining granules in their cytoplasm on light microscopy. ... Obligate intracellular parasites are organisms that cannot reproduce outside their host cell. ... Phosphatidylserine is a phospholipid nutrient found in fish, green leafy vegetables, soybeans and rice, and is essential for the normal functioning of neuronal cell membranes. ... Respiratory burst is the rapid release of reactive oxygen species (superoxide radical and hydrogen peroxide) from different types of cells. ... This article does not cite any references or sources. ... White Blood Cells is also the name of a White Stripes album. ... MONOCYTES: Plural of monocyte. ... Natural killer cells (NK) are a type of lymphocyte (a white blood cell) and a component of nonspecific immune defense. ... Interferon-gamma or IFN-g is a dimerized soluble cytokine which is a Type II Interferon. ... This article does not cite any references or sources. ...

Persistency and attraction

The lifespan of neutrophil granulocytes is quite short. They circulate in bloodstream for about 6 or 10 hours after leaving bone marrow, whereupon they undergo spontaneous apoptosis. Microbial pathogens have been reported to influence cellular apoptosis by different strategies. Obviously because of the inhibition of caspase3-activation Leishmania major can induce the delay of neutrophils apoptosis and extend their lifespan for at least 2–3 days. The fact of extended lifespan is very beneficial for the development of infection because the final host cells for these parasites are macrophages, which normally migrate to the sites of infection within 2 or 3 days. The pathogens are not dronish; instead they take over the command at the primary site of infection. They induce the production by PMN of the chemokines MIP-1α and MIP-1ß (macrophage inflammatory protein) to recruit macrophages. Neutrophil granulocytes (commonly referred to as neutrophils) are a class of white blood cells and are part of the immune system. ... Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ... This article does not cite any references or sources. ... Caspases are a group of cysteine proteases, enzymes with a crucial cysteine residue that can cleave other proteins after an aspartic acid residue, a specificity which is unusual among proteases. ... Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. ...

Silent phagocytosis

To save the integrity of the surrounding tissue from the toxic cell components and proteolytic enzymes contained in neutrophils, the apoptotic PMN are silently cleared by macrophages. Dying PMN expose the "eat me"-signal phosphatidylserine which is transferred to the outer leaflet of the plasma membrane during apoptosis. By reason of delayed apoptosis the parasites that persist in PMN are taken up into macrophages, employing an absolutely physiological and non-phlogistic process. The strategy of this "silent phagocytosis" has following advantage for the parasite: Toxic redirects here, but this is also the name of a song by Britney Spears; see Toxic (song) Look up toxic and toxicity in Wiktionary, the free dictionary. ... Proteolysis is the directed degradation (digestion) of proteins by cellular enzymes called proteases or by intramolecular digestion. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... Phosphatidylserine is a phospholipid nutrient found in fish, green leafy vegetables, soybeans and rice, and is essential for the normal functioning of neuronal cell membranes. ... Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Physiology (in Greek physis = nature and logos = word) is the study of the mechanical, physical, and biochemical functions of living organisms. ...

• Taking up apoptotic cells silences macrophage killing activity leading to a survival of the pathogens.

• Pathogens inside of PMN have no direct contact to the macrophage surface receptors, because they can not see the parasite inside the apoptotic cell. So the activation of the phagocyte for immune activation does not occur. Receptor may refer to: In telecommunication, a receiver. ...

Literature:

Zandbergen et al. "Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum", PNAS, Sept. 2006

Laskay et al. "Neutrophil granulocytes - Trojan horses for "Leishmania major" and other intracellular microbes?", TRENDS in microbiology, May 2003

References

Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 146th day of the year (147th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 146th day of the year (147th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 146th day of the year (147th in leap years) in the Gregorian calendar. ...

External links

• The International Leishmania Network (ILN) has basic information on the disease and links to many aspects of the disease and its vector.

• A discussion list (Leish-L) is also available with over 600 subscribers to the list, ranging from molecular biologists to public health workers, from many countries both inside and outside endemic regions. Comments and questions are welcomed.

• KBD: Kinetoplastid Biology and Disease, is a website devoted to leishmaniasis, sleeping sickness and Chagas (American leishmaniasis). It contains free access to full length peer review articles on these subjects. The site contains many articles relating to the unique kinetoplastid organelle and genetic material therein.