Leishmania Mechanisms of Evasion

Leishmaniasis, caused by protozoan parasites of the Leishmania genus, is an infection encountered in tropical and subtropical regions of the world. Leishmania parasites are propagated by different species of the sandfly vector (genus Phlebotomus or Lutzomya), depending on the region. Old World species of Leishmania, such as L. donovani and L. major, cause pathology from southern Europe to Africa, the Middle East, and throughout southern Asia, whereas New World species (e.g., L. mexicana, L. amazonensis, and L. chagasi) are found throughout South and Central America and as far north as the southern states of the United States. Clinical manifestations differ widely, depending on the Leishmania species. The majority of mortality results from the visceral form of leishmaniasis, caused by L. donovani or L. chagasi; 90% of annual cases are reported in Bangladesh, Brazil, India, Nepal, and Sudan. The most common manifestations are cutaneous lesions; 90% of new cases of cutaneous leishmaniasis occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia, and Syria, and they are caused principally by L. major and the L. Mexicana subgenus(Who, 2002; Herwaldt et al ,1999) .In its mammalian host, the lifestyle of Leishmania is that of an obligate intracellular pathogen infecting the hematopoietic cells of the monocyte/macrophage lineage, which it enters by phagocytosis. Since this cell type is specialized for the destruction of invading pathogens and priming of the host immune response, Leishmania has had to evolve a range of sophisticated mechanisms to subvert normal macrophage function( David sacks et al ;2002 ;m.zand et al,2013; C. Bogdan et al, 1999 ). In this review, we focus on the molecular mechanisms whereby Leishmania can subvert host surveillance by altering the macrophage signal transduction machinery, thereby modulating the macrophage environment in its favor. It should be noted that studies generally use only one, or sometimes two, species of Leishmania at a time and a single developmental stage, and this gives the impression that the mechanisms revealed apply to all species. However, given the diversity of pathologies caused by Leishmania spp., it is inevitable that significant differences exist in the mechanisms of host cell manipulation. These differences may account for some of the conflicting results described in this review; our understanding is now at a stage where more studies directly comparing the effects of different species on macrophages would be extremely useful.