Leishmaniasis and Arginase Activity

Leishmaniasis is a vector-born disease, which causes uncontrolled parasite (Leishmania) growth. This disease is predominantly seen in children and is “endemic in almost all tropical and subtropical areas” (Muller, et.al. e235). Leishmania predominantly live in macrophages, in which the macrophages can control the growth and production of these parasites through two enzymes, NOS2 and arginase. Furthermore, these macrophages are M2 macrophages, which are regulated by Th2 cells. These researchers have shown that increased arginase activity leads to non-stop parasite growth as well pathology in vivo (e235).

Researchers hypothesize that arginase activity is increased in children, which accounts for the severity of Leishmanisis in children. Balb/c mice were used in various age ranges and were infected with Leishmanisis and then tested to determine arginase levels. The researchers showed the younger mice had increased levels of arginase than the older mice. Furthermore, the younger mice had more exacerbated pathology as well as increased severity of lesions. Because Balb/c mice lack the proper Th1 response in the presence of Leishmania, the researchers performed several other experiments to show that the improper regulation of Th1 was not the cause of the increased parasitic growth. They were able to show that the decrease in arginase activity with age is responsible for the the severity of Leishmaniasis in children.

This article is interesting because it shows the older people are less prone to this disease than children, which is generally the opposite of most diseases since ageing results in a decrease in immune responses. However, arginase is also known to play an important role in wound healing. One would expect that children would have an increase in arginase due to their more active lifestyles and because they generally get hurt a lot more than older people. This makes me think that at one point, arginase might not have been the primary cause of parasite overgrowth, but it evolved into a parasite growth promoter.

Also, it seems that there would be even more severe problems in children that lacked the proper M1, classically-activated macrophages because they would not be able to destroy the parasites and control the infection. This would make it nearly impossible for M2 macrophages to try to help with the healing process. Although, there is paper doesn't show a correlation between the Th phenotype and the severity of the disease, I wonder whether all people with Leishmanisis might have reduced efficiency of their M1 macrophages, which contributes the overall problem with the disease.


"Age-related alteration of arginase activity impacts on severity of leishmaniasis." Müller I, Hailu A, Choi BS, Abebe T, Fuentes JM, Munder M, Modolell M, Kropf P.PLoS Neglected Tropical Diseases. 2008 May 14;2(5):e235.