Leishmania
| Leishmania | ||||||||||||
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Leishmania tropica |
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| Scientific name | ||||||||||||
| Leishmania | ||||||||||||
| Ross , 1903 |
As Leishmania ( Leishmania, by William Boog Leishman named) refers to a genus of flagellated protozoa which in the blood in macrophages proliferate ( haemoflagellates ). Leishmanias live as intracellular parasites with a host change between insects ( sand flies , butterfly flies ) and vertebrates ( sheep , dogs , humans ).
The clinical picture caused by leishmania is called leishmaniasis .
distribution
Leishmanias are common all over the world with the exception of Australia. They are considered to be the cause of many animal diseases . Fewer species infest humans. According to WHO estimates, there are around 1.5 million new cases of cutaneous leishmaniasis and around 500,000 of visceral leishmaniasis worldwide each year. About twelve million people are currently infected with leishmania.
features
Like all flagellates , Leishmanias change their shape and the position of the flagellum depending on the host and stage of development (see: Trypanosomes ). However, the leishmanias are somewhat smaller on average ( promastigote : 20 micrometers , amastigote : 2 µm).
Life cycle
The multiplication of the Leishmania takes place in two hosts . When the sandfly bites, promastigote (flagellated) forms are released from the saliva , which are phagocytosed by a macrophage (phagocyte) in the vertebrate (passive invasion) and there transform into an amastigote (non-flagellated) form. In the macrophage, multiplication takes place through division. After the host cell is destroyed, the amastigote forms are released and are able to invade other macrophages. If a sand mosquito ingests the pathogen from tissue or blood, the cycle is closed. In the mosquito intestine, the leishmanias change back to the promastigotic form. This migrates via an amastigote form in the intestinal epithelium into the mosquito's salivary gland and infection can occur again.
Harmful effect
Among the diseases caused by Leishmania (Leishmaniasis), a distinction is made between cutaneous forms (" Oriental bump ") and visceral forms ("Kala Azar"). In the case of the oriental bump, the leishmanias prefer to settle in macrophages under and in the skin tissue. This is usually not fatal. However, if they penetrate internal organs (spleen, liver, intestines, lymph nodes and bone marrow) and attack macrophages there, symptoms of hepatosplenomegaly (abnormal enlargement of the spleen and liver) can occur, which if left untreated in 90% of cases due to blood clotting disorders and additional secondary infections are fatal. Overcoming leishmaniasis leads to long-term or lifelong immunity.
The course of leishmaniasis is very dependent on the patient's immune status. In HIV patients there are often infections with few symptoms (without splenomegaly), which, despite therapy and prevention of recurrence, show a mean survival of about one year. The frequency of fatal infections is very high, especially with additional malnutrition.
See also : Parasites of humans
Infection process in detail
Neutrophils - Trojan horses for leishmania
The strategy of the "Trojan horse" as a pathogenicity factor of intracellular microorganisms is to skilfully bypass the immune defense and its memory function by means of macrophages - clearance of neutrophilic granulocytes that carry a "no danger" signal on their surface through apoptosis .
The parasites of the species Leishmania major transmitted by the sand mosquito corrupt the action of the first defense reactions of their host organism for their own benefit and reverse them from eating / inflammation / killing to eating / no inflammation / no killing. They make decisive use of the phagocytosis-friendly polymorphonuclear neutrophil granulocytes (PMN) for a tricky game of hide-and-seek, in which they attack the long-lived macrophages undetected by the immune system in order to multiply there.
Admission and Survival
When infected with microorganisms in the tissue, PMNs escape from the bloodstream and migrate, attracted by chemokines, into the affected area (skin after an insect bite). There they immediately begin their work as the “first immune defense front” and phagocytize the intruders due to their foreign, activating surface structures. This creates a local inflammatory process. Activated PMNs secrete chemokines , especially IL-8, which attract more granulocytes and stimulate phagocytosis . In addition, in the case of a leishmania infection, already phagocytosed leishmania promote the formation of IL-8 by PMN. In terms of parasites, this sounds illogical at first. However, this mechanism is also found in other obligatory and facultative intracellular microorganisms. There are several ways for such pathogens to survive within a cell . Surprisingly, the co-injection of apoptotic and live pathogens causes a far more fulminant course of the disease than the sole injection with live parasites. The anti-inflammatory signal phosphatidylserine , which is normally found on the surface of apoptotic cells, switches off the oxidative burst of the granulocytes, which occurs in Leishmania major , which is why there is no killing or degradation of the living pathogens. An increase in the granulocytes does not take place, but the pathogens can persist in the primarily infected tissue without being recognized and therefore unchecked. Furthermore, the promastigotic forms of Leishmania are able to produce a certain chemokine, the Leishmania chemotactic factor (LCF), which increases the chemotaxis for PMN, but not for other leukocytes ( NK cells , monocytes ). For this purpose, the formation of the interferon-inducible chemokine CXCL 10 in the infected PMN is stopped, which additionally prevents the activation of NK and Th1 cells . During phagocytosis, the parasites stay alive because their primary host cells (PMN) signal “no pathogen” through the development of apoptotic cell associated molecular patterns (ACAMP).
Persist and attract
The natural lifespan of granulocytes is relatively short, averaging 6 to 10 hours in the peripheral blood, after which they undergo spontaneous apoptosis . In infected PMNs with the genus Leishmania major , it was observed that the time until apoptosis is increased by about 2 to 3 days by inhibiting caspase-3 activation. This favors the course of the infection, since the actual host cells of the leishmania, the macrophages, in which reproduction and development also take place, only migrate into the inflammatory tissue 2 to 3 days after the PMN. The parasites also cause the granulocytes to release the chemokines MIP-1α / CCL3 and MIP-1β / CCL4 (macrophage inflammatory protein) in order to attract the macrophages.
"Silent Phagocytosis"
In order to protect the integrity of the surrounding tissue from the cell toxins and proteolytic enzymes from the granulocytes, the apoptotic PMNs are cleared away by macrophages. The “eat me” signal is represented here by phosphatidylserine , which is transferred to the outside of the cytoplasmic membrane in the process of apoptosis . Due to the delayed apoptosis, the leishmanias that persist in the PMN are ultimately taken up by the macrophages via a completely physiological clearing process. The path via this "quiet phagocytosis" has the following advantages for the infection:
- The uptake of apoptotic material dampens the macrophage activity, which means that no defense mechanisms against the intracellular parasite are activated and the pathogens survive.
- Pathogens located intracellularly in PMN have no direct contact with the macrophage surface receptors, as these do not perceive the parasite within the apoptotic cell. Thus there is no activation of the phagocytes and the immune system.
species
- Leishmania aethiopica
- Leishmania donovani
- Leishmania enriettii
- Leishmania infantum
- Leishmania major
- Leishmania mexicana
- Leishmania amazonensis
- Leishmania tropica
- Leishmania tarentolae
- Paleoleishmania proterus. The genus Paleoleishmania was established as a collective taxon for fossil Trypanosomatida, which are associated with sand flies. In Cretaceous Burmese amber, blood was found inside the body of a sand fly and a mosquito containing microbes thathave been describedas Paleoleishmania proterus . This finding gave rise to speculation that the pathogen may have contributed to the extinction of dinosaurs.
literature
Article base
- Thomas Berg, Norbert Suttorp (ed.): Infectious diseases. [understand, recognize, treat]; 93 tables. Thieme, Stuttgart 2004, ISBN 978-3-13-131691-2 .
- Helmut Hahn, Hahn-Falke-Kaufmann-Ullmann, Paul Klein, Konstanze Vogt: Medical microbiology and infectious diseases. 5th, fully updated edition, Springer, Berlin / Heidelberg 2005, ISBN 978-3-540-21971-2 .
Continuing
- Ger van Zandbergen et al: "Leishmania" disease development depends on the presence of apoptotic promastigotes in the virulent inoculum. In: Proceedings of the National Academy of Sciences . (PNAS) Vol. 103, No. 37, Sept. 2006, ISSN 0027-8424 , pp. 13837-13842, doi : 10.1073 / pnas.0600843103 .
- T. Laskay, G. van Zandbergen, W. Solbach: Neutrophil granulocytes - Trojan horses for "Leishmania major" and other intracellular microbes? In: Trends in microbiology. Vol. 11, No. 5, May 2003, ISSN 0966-842X , pp. 210-214.
Individual evidence
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^ WHO : Leishmaniasis - The disease and its epidemiology . On: who.int ; last accessed on June 22, 2014.
- ^ A. Ross: Amber - The Natural Time Capsule. London 2009, ISBN 978-0-565-09258-0 .
- ↑ G. Poinar Jr. & R. Poinar, Evidence of Vector-Borne Disease of Early Cretaceous Reptiles. In: Vector-Borne and Zoonotic Diseases , Vol. 4 (4), 2004, ISSN 1530-3667, pp. 281-284.
