The Result When Phagocytosis Fails

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a) a photo of a man with large skin lesions covering his face b) A macrophage in a field of red blood cells. The macrophage has many smaller circles inside of it. Each of these has a distinct nucleus.
(a) Cutaneous leishmaniasis is a disfiguring disease caused by the intracellular flagellate Leishmania tropica, transmitted by the bite of a sand fly. (b) This light micrograph of a sample taken from a skin lesion shows a large cell, which is a macrophage infected with L. tropica amastigotes (arrows). The amastigotes have lost their flagella but their nuclei are visible. Soon the amastigotes will lyse the macrophage and be engulfed by other phagocytes, spreading the infection. (credit a: modification of work by Otis Historical Archives of “National Museum of Health & Medicine”; credit b: modification of work by Centers for Disease Control and Prevention)

OpenStax Microbiology

Although phagocytosis successfully destroys many pathogens, some are able to survive and even exploit this defense mechanism to multiply in the body and cause widespread infection. Protozoans of the genus Leishmania are one example. These obligate intracellular parasites are flagellates transmitted to humans by the bite of a sand fly. Infections cause serious and sometimes disfiguring sores and ulcers in the skin and other tissues. Worldwide, an estimated 1.3 million people are newly infected with leishmaniasis annually.

Salivary peptides from the sand fly activate host macrophages at the site of their bite. The classic or alternate pathway for complement activation ensues with C3b opsonization of the parasite. Leishmania cells are phagocytosed, lose their flagella, and multiply in a form known as an amastigote (Leishman-Donovan body) within the phagolysosome. Although many other pathogens are destroyed in the phagolysosome, survival of the Leishmania amastigotes is maintained by the presence of surface lipophosphoglycan and acid phosphatase. These substances inhibit the macrophage respiratory burst and lysosomal enzymes. The parasite then multiplies inside the cell and lyses the infected macrophage, releasing the amastigotes to infect other macrophages within the same host. Should another sand fly bite an infected person, it might ingest amastigotes and then transmit them to another individual through another bite.

There are several different forms of leishmaniasis. The most common is a localized cutaneous form of the illness caused by L. tropica, which typically resolves spontaneously over time but with some significant lymphocyte infiltration and permanent scarring. A mucocutaneous form of the disease, caused by L. viannia brasilienfsis, produces lesions in the tissue of the nose and mouth and can be life threatening. A visceral form of the illness can be caused by several of the different Leishmania species. It affects various organ systems and causes abnormal enlargement of the liver and spleen. Irregular fevers, anemia, liver dysfunction, and weight loss are all signs and symptoms of visceral leishmaniasis. If left untreated, it is typically fatal.

Source:

Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology

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