pntd-0001019-g002: L. infantum-specific CD4+ T cell proliferative responses in vertically-infected pups.Peripheral blood mononuclear cells (PBMC) were isolated from blood samples from neonatal pups (4–7), 3-month-old pups (A–D) and the dam. PBMC were stained with CFSE and cultured in the presence of L. infantum freeze-thawed antigen. PMBC were harvested at day 7 and the CD4+ T cell proliferation response was assessed via flow cytometry. Shown are the percentages of proliferating CD4+ T cells in response to L. infantum antigen.

Mentions: Whole blood samples from the dam, pups 4–7 and A–D were collected prior to euthanasia. Peripheral blood mononuclear cells (PBMC) were isolated, stained with CFSE, and stimulated with concanavalin A (ConA), L. infantum antigen, or were left untreated. PMBC were analyzed for CD4+ T cell proliferation via flow cytometry. CD4+ T cells from all dogs proliferated in response to stimulation with ConA, indicating that the CD4+ T cell compartment was not mitogenically deficient (data not shown), as previously indicated [7]. In response to L. infantum antigen stimulation all dogs excluding pups A and 7, had strong antigen-specific CD4+ T cell proliferative responses (Figure 2). These data suggest that despite likely in utero transmission, these pups were able to mount antigen-specific adaptive immune response at birth and were neither naïve nor immune-tolerant to L. infantum antigen.

Boggiatto PM, Gibson-Corley KN, Metz K, Gallup JM, Hostetter JM, Mullin K, Petersen CA - PLoS Negl Trop Dis (2011)

Bottom Line: Zoonotic visceral leishmaniasis (ZVL) is an emerging problem in some U.S. dog breeds, with an annual quantitative PCR prevalence of greater than 20% within an at-risk Foxhound population.Several reports have indicated that endemic ZVL may be transmitted vertically.Our aims for this present study were to establish whether vertical/transplacental transmission was occurring in this population of Leishmania-infected US dogs and determine the effect that this means of transmission has on immune recognition of Leishmania.A pregnant L. infantum-infected dam donated to Iowa State University gave birth in-house to 12 pups.This is the first report of vertical transmission of L. infantum in naturally-infected dogs in North America, emphasizing that this novel means of transmission could possibly sustain infection within populations.Evidence that vertical transmission of ZVL may be a driving force for ongoing disease in an otherwise non-endemic region has significant implications on current control strategies for ZVL, as at present parasite elimination efforts in endemic areas are largely focused on vector-borne transmission between canines and people.

Affiliation: Immunobiology Program, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.

Abstract: Dogs are the predominant domestic reservoir for human L. infantum infection. Zoonotic visceral leishmaniasis (ZVL) is an emerging problem in some U.S. dog breeds, with an annual quantitative PCR prevalence of greater than 20% within an at-risk Foxhound population. Although classically Leishmania is transmitted by infected sand flies and phlebotomine sand flies exist in the United States, means of ongoing L. infantum transmission in U.S. dogs is currently unknown. Possibilities include vertical (transplacental/transmammary) and horizontal/venereal transmission. Several reports have indicated that endemic ZVL may be transmitted vertically.Our aims for this present study were to establish whether vertical/transplacental transmission was occurring in this population of Leishmania-infected US dogs and determine the effect that this means of transmission has on immune recognition of Leishmania.A pregnant L. infantum-infected dam donated to Iowa State University gave birth in-house to 12 pups. Eight pups humanely euthanized at the time of birth and four pups and the dam humanely euthanized three months post-partum were studied via L. infantum-kinetoplast specific quantitative PCR (kqPCR), gross and histopathological assessment and CD4+ T cell proliferation assay.This novel report describes disseminated L. infantum parasites as identified by kqPCR in 8 day old pups born to a naturally-infected, seropositive U.S. dog with no travel history. This is the first report of vertical transmission of L. infantum in naturally-infected dogs in North America, emphasizing that this novel means of transmission could possibly sustain infection within populations.Evidence that vertical transmission of ZVL may be a driving force for ongoing disease in an otherwise non-endemic region has significant implications on current control strategies for ZVL, as at present parasite elimination efforts in endemic areas are largely focused on vector-borne transmission between canines and people. Determining frequency of vertical transmission and incorporating canine sterilization with vector control may have a more significant impact on ZVL transmission to people in endemic areas than current control efforts.