Leishmania

Leishmania tropica

• Leishmania aethiopica
• Leishmania donovani
• Leishmania infantum
• Leishmania major
• Leishmania mexicana
• Leishmania amazonensis
• Leishmania tropica
• Leishmania tarentolae

As Leishmania ( Leishmania, by William Boog Leishman named ) refers to a genus of flagellated protozoa that multiply in the blood macrophages ( haemoflagellates ). Leishmania live as obligate intracellular parasite with a host change between insects ( sand flies, sandflies ) and vertebrates (sheep, dogs, humans ).

The disease caused by Leishmania is known as leishmaniasis.

Dissemination

They are widespread in Australia to all over the world and are considered the catalyst of many animal diseases. Man is attacked by fewer species. The WHO estimates that there are about 1.5 million new cases annually worldwide to cutaneous leishmaniasis and 500,000 visceral leishmaniasis. About 12 million people are currently infected with Leishmania.

Features

How they change all flagellates their shape and the position of the scourge depending on the host and stage of development (see: trypanosomes ). However, the Leishmania on average slightly smaller ( promastigote: 20 micron, amastigote: 2 microns ).

Life cycle

The proliferation of Leishmania occurs in two hosts. From the sandfly be submitted with the saliva during stitch promastigote ( flagellated ) forms in the vertebrate from macrophages ( phagocytes ) are phagocytosed (passive invasion ) and are converted there into an amastigote ( unbegeißelte ) form. In the macrophage multiplication takes place by division. After destruction of the host cell, the amastigote forms are free and are able to penetrate into other macrophages. If a sandfly the pathogen from the tissue or the blood on, the circuit is closed. In the mosquito gut, the Leishmania convert back to the promastigote form. These moves over a again amastigote form in the intestinal epithelium now in the salivary gland of the mosquito and again can be an infection.

Harmful effect

The diseases that are caused by Leishmania ( Leishmania ), one distinguishes between cutaneous forms ( " oriental sore " ) and visceral forms ( " kala azar "). In the oriental sore, the Leishmania settle preferentially in macrophages and in the skin tissue. This usually runs not fatal. If they penetrate into internal organs (spleen, liver, intestine, lymph nodes and bone marrow) and infest there macrophages, it can cause hepatosplenomegaly symptoms ( abnormal enlargement of the spleen and liver ) may occur, untreated in 90 % of cases by bleeding disorders and additional secondary infections are fatal. Having had leishmaniasis leads to a prolonged or lifelong immunity.

The course of leishmaniasis is very dependent on the immune status of the patient. In HIV patients, there are often few symptoms extending infections ( without splenomegaly), the show despite treatment and prevention of relapse a median survival of about one year. The incidence of fatal infections is very high especially with additional malnutrition.

See also: parasites of humans

Neutrophil granulocytes - Trojan horses for Leishmania

The strategy of the " Trojan Horse " as a virulence factor of intracellular microorganisms is sent by macrophage clearance of neutrophils, which carry through apoptosis, a " no danger " signal on their surface, the immune system and its memory function to get around.

The data transmitted by the sand fly parasites of the species Leishmania major corrupting effect of the first defense reactions of their host organism for their own benefit and return it by eating / inflammation / killing after eating / no ignition / no killing to. They make the phagozytosefreudigen polymorphonuclear neutrophils (PMN ) is crucial to benefit a tricky game of hide where they undetected by the immune system attacked the long-lived macrophages to multiply there.

Uptake and survival

With an infection with microorganisms in the tissue PMN emerge from the bloodstream and migrate, attracted by chemokines, in the affected area ( skin after insect bite ), a. There, they immediately begin their work as "first immune defensive front " and phagocytose the invaders due to their strange, activating surface structures. This produces a local inflammatory process. Activated PMN secrete chemokines now, especially IL- 8, which further attract granulocytes and stimulate phagocytosis. In addition, already promote at a phagocytosed Leishmania leishmania the production of IL -8 by PMN. For the purposes of the parasites first this sounds illogical. This mechanism but can be found in other obligate and facultative intracellular microorganisms. For such pathogens, there are several ways to survive within a cell. Surprisingly, the co-injection of apoptotic and living organisms caused a much more fulminant course of the disease as the sole injected with live parasites. The anti-inflammatory signal normally found on the surface of apoptotic cells, phosphatidylserine on, occurring in Leishmania major, the oxidative burst of granulocytes, which is why no killing and no degradation of the living pathogen occurs. An increase in the granulocytes does not take place, however, the pathogen can persist as unrecognized and therefore without fighting in the primary infected tissue. Furthermore, the promastigote forms of Leishmania is capable of producing a particular chemokine, the Leishmania chemotactic factor ( LCF), which increases the chemotaxis of PMN, but not for other leucocytes ( NK cells, monocytes). , The formation of the interferoninduzierbaren chemokine CXCL 10 is stopped in the infected PMN, which also prevents the activation of NK cells and Th1. During phagocytosis, the parasites remain alive, as their primary host cells ( PMN) " no agent" signaling by the expression of apoptotic cell -associated molecular patterns ( ACAMP ).

Persistence and attracting

The natural life span of granulocytes is relatively short and is on average 6 to 10 hours in the peripheral blood, after which they undergo spontaneous apoptosis. In infected PMN to the genus Leishmania major has been observed that apoptosis susceptibility significantly, by about 2 to 3 days, will prolong influenced by an inhibition of caspase-3 activation. This fact is particularly favorable for the course of infection, since the actual host cells of Leishmania, macrophages, in which the multiplication and development takes place, only 2 to 3 days after the PMN migrate into the inflamed tissue. The parasites lurk not just stand at their point of entry, but cause the granulocytes to the chemokines MIP- 1α / CCL3 and MIP- 1β / CCL4 ( macrophage inflammatory protein) to distribute in order to attract the macrophages.

"Silent Phagocytosis "

To protect the integrity of the surrounding tissue from the cytotoxins and proteolytic enzymes of the granulocytes, which are apoptotic PMN cleared by macrophages. The " eat me " signal is shown here of phosphatidylserine which rearranges in the process of apoptosis on the outside of the cytoplasmic membrane. Due to the delayed apoptosis in PMN persistent Leishmania eventually be included on a completely physiological Abräumgeschehen by the macrophages. The way this " silent phagocytosis " now has the following advantages for the infection:

• The uptake of apoptotic material dampens macrophage activity, thereby no defense mechanisms against intracellular parasites are activated and survive the pathogen.
• Intracellular pathogens lying in PMN have no direct contact with the macrophage surface receptors, since these do not "see" the enemy within the apoptotic cell. Thus there is no activation of the phagocyte and the immune system.

Swell

• N. Suttorp, M. Mielke et al. Infectious diseases. Thieme, Stuttgart, 2004.
• H. Hahn, D. Falke et al.: Medical Microbiology and Infectious Diseases. 5th edition, Springer, Berlin / Heidelberg, 2004.