Research has shown yet another component in our body's immune system that could prove vital in controlling Leishmaniasis. This time, our body's memory T cells are the main players in controlling this terrible condition. So far, it is understood that after a VIRAL infection, memory T cells are formed, which will result in a quicker and more effective immune response during a reinfection by the virus. A new study has shown that the same mechanism also applies after a PARASITIC infection, opening new doors in research for ways to combat and control Leishmaniasis, amongst other diseases. There are 2 kinds of T cells, CD4 and CD8 T cells. CD4 T cells assist in the immune response by activating other immune cells, while CD8 T cells are able to kill pathogens directly. Following an infection, a population of T cells that survive become memory T cells, which circulate around the body. However, it is suspected that these circulating memory T cells are not the only way the body protects against immunity... After transferring CD4 T cells from a mouse that has recovered from Leishmaniasis to another mouse who has never contracted the disease, it was observed that the latter only received PARTIAL protection, which led researchers to suspect another element was missing from the equation. By observing more mice who had recovered from Leishmaniasis, researchers discovered parasite-specific T cells in the skin, not only from the site of infection, but other sites as well. Further studies showed that these T cells were unlike the memory T cells which circulated around the body after an infection, they were actually residents of the skin! These resident CD4 memory T cells are also able to recruit other T cells to the site of infection, a key process in fighting off infections.
Mice that received tissue-resident CD4 cells via a skin graft from mice previously infected with Leishmaniasis, when given an injection of Leishmania-responsive T cells, were able to respond to an infection as effectively as a mouse that has developed natural immunity. This hints at a possibility of a vaccine through a method similar to that of the Smallpox vaccine, via a process known as scarification, which involves scratching the skin. This effectively generates tissue-resident memory cells.
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There has been extreme difficulty treating patients positive for both visceral leishmaniasis and HIV. Both diseases affect the immune system of the patients and are fatal if left untreated. As if tackling a single disease isn't enough, now patients would have to deal with 2! The risk of death for patients with visceral leishmaniasis co-infected with HIV is 9x higher. Visceral leishmaniasis also causes the progression of HIV to speed up, and relapses of the disease is more common in patients co-infected with HIV. Chances of curing visceral leishmaniasis are also significantly lower. A study in India treated patients with confirmed visceral leishmaniasis-HIV co-infections with a combination of drugs, amphotericin B and miltefosine, and encouraged to start on antiretrovial therapy.
102 patients were followed-up for an average of 11 months, and from the results of the study, combination therapy appeared to be a safe and effective way for treatment of visceral leishmaniasis in HIV co-infected individuals. Inflammasomes are important structures of our immune system in combating pathogens. Their effect on bacterial and viral pathogens are well studied, while in contrast, their effect on protozoan parasites, such as Leishmania, are less studied [1]. However, research led by scientists at St. Jude Children Hospital have led to surprising revelations about resistance against Leishmaniasis. Studies were carried out on mice infected with Leishmaniasis. As part of the body's immune response, NLRP3 inflammasomes sense Leishmania parasites and produce interleukin 18 (IL-18), messenger molecules involved in the body's first line of defence against diseases. Surprisingly, inhibiting IL-18 protected specially bred mice from the most common form of Leishmaniasis instead of aggravating the disease. Scientists had expected, based on previous studies with a different mouse model of Leishmaniasis, for IL-18 to induce an immune response, resulting in production of molecules involved in protection against Leishmaniasis. However, the opposite happened, and IL-18 induced the production of interleukin 4 (IL-4), which skewed the immune response in the parasite's favour instead [2]. Thus, by inhibiting NLRP3 inflammasomes, IL-18 production declined and the mice were resistant towards the infection. In conclusion, neutralizing IL-18 protected mice against Leishmaniasis, suggesting that the same might be able to be done for humans.
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August 2015
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