The immunological, environmental, and phylogenetic perpetrators of metastatic leishmaniasis

Abstract

Cutaneous leishmaniases have persisted for centuries as chronically disfiguring parasitic infections affecting millions of people across the subtropics. Symptoms range from the more prevalent single, self-healing cutaneous lesion to a persistent, metastatic disease, where ulcerations and granulomatous nodules can affect multiple secondary sites of the skin and delicate facial mucosa, even sometimes diffusing throughout the cutaneous system as a papular rash. The basis for such diverse pathologies is multifactorial, ranging from parasite phylogeny to host immunocompetence and various environmental factors. Although complex, these pathologies often prey on weaknesses in the innate immune system and its pattern recognition receptors. This review explores the observed and potential associations among the multifactorial perpetrators of infectious metastasis and components of the innate immune system.

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis

“…Discovered in the 1980s (7,8), and since then for a long time neglected, Leishmaniavirus is a genus of double-stranded RNA viruses belonging to the Totiviridae family. Like most other viruses in this family, LRV1 is neither shed nor infectious, and thus can be seen as a persistent, endogenous viral element (9). Two species of LRV have been identified.…”

Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response

“…One recently identified parasite factor contributing to disease severity in Leishmania guyanensis is the RNA virus Leishmaniavirus (6,7). This virus is a member of the Totiviridae family and consists of a single-segmented dsRNA genome that encodes only a capsid protein and an RNA-dependent RNA polymerase (RDRP) (8,9).…”

“…This virus is a member of the Totiviridae family and consists of a single-segmented dsRNA genome that encodes only a capsid protein and an RNA-dependent RNA polymerase (RDRP) (8,9). It is most frequently found (as LRV1) in New World parasite species in the subgenus Viannia, such as Leishmania braziliensis (Lbr) and L. guyanensis (Lgy), which cause both cutaneous and mucocutaneous disease (6), but it has also been found sporadically in Old World subgenus Leishmania species (as LRV2) (10,11). Like most totiviruses, LRV1 is neither shed nor infectious, and it thus can be viewed as a long-term evolutionary endosymbiont whose activities on the mammalian host arise indirectly through the parasite, rather than by direct infection of the mammalian host by the virus (6).…”

“…It is most frequently found (as LRV1) in New World parasite species in the subgenus Viannia, such as Leishmania braziliensis (Lbr) and L. guyanensis (Lgy), which cause both cutaneous and mucocutaneous disease (6), but it has also been found sporadically in Old World subgenus Leishmania species (as LRV2) (10,11). Like most totiviruses, LRV1 is neither shed nor infectious, and it thus can be viewed as a long-term evolutionary endosymbiont whose activities on the mammalian host arise indirectly through the parasite, rather than by direct infection of the mammalian host by the virus (6). Previous work has shown that mice infected with LRV1-bearing strains of Lgy exhibit greater footpad swelling and higher parasitemia than mice infected with LRV1-negative Lgy (7).…”

Diagnostic Efficacy of Molecular Techniques for Detection and Identification of Leishmania Species in Human Whole Blood and Skin Samples from Ecuador

“…3 CL is a common form of the disease characterized by the appearance of a localized skin lesion at the site of the vector-bitten area. 5 In 5-20% of CL, the infection progresses to MCL, due to the dissemination of the parasite in the bloodstream, the lymphatic system, or by direct extension to mucosal membranes. 6 A total of 15 species of Leishmania have been identified as responsible for the infection of humans.…”