Leishmaniasis, Tegumentary, Susceptibility To

Tegumentary leishmaniasis due to the parasite Leishmania braziliensis occurs in 2 stages after the infected sandfly bite: (1) a primary cutaneous lesion followed by (2) a secondary mucosal involvement generally resulting in severe facial deformities. To assess genetic and environmental factors involved in the development of the cutaneous lesion, Alcais et al. (1997) performed a family study in a region of Bolivia where the disease is endemic. This study involved 118 nuclear families, each with at least 1 cutaneous affected subject; 41 families were of native origin, and 77 (designated 'migrant') had recently settled in the area. The investigators concluded that in the 77 migrant families a recessive major gene controlled the onset of the primary cutaneous lesion, with residual familial dependencies and age-genotype interaction. Penetrance estimation showed that young subjects were genetically more susceptible than older subjects, suggesting that this genetic component could concern mechanisms involved in the development of individual protection during childhood. There was a significant genetic heterogeneity according to the native or migrant origin of the families, and no major-gene effect was found in the native subsample.

Leishmania parasites in Latin America cause cutaneous (CL) and mucocutaneous leishmaniasis (MCL). MCL is associated with persistent inflammatory immune responses. Parasites from MCL patients reproduce the metastatic phenotype in a hamster model. Using DNA microarray analysis and metastatic and nonmetastatic Leishmania guyanensis clones in infected and uninfected mouse bone marrow-derived macrophages, Ives et al. (2011) observed increased expression of Ccl5 (187011), Cxcl10 (147310), Ifnb (147640), Tnf (191160), and Il6 (147620) after infection with metastatic parasites compared with nonmetastatic parasites or parasites obtained from CL patients. Induction of these proinflammatory cytokines and chemokines occurred in a Tlr3 (603029)- and Trif (TICAM1; 607601)-dependent manner. Metastatic L. guyanensis expressed higher levels of a Leishmania double-stranded RNA virus, LRV1, and this virus alone induced high chemokine and cytokine expression. Mice lacking Tlr3 had decreased parasite burden and footpad swelling after infection compared with wildtype mice. Ives et al. (2011) concluded that recognition of LRV1 within metastatic Leishmania parasites promotes inflammation and subverts the immune response to Leishmania, leading to parasite persistence.