Immunologic progression of canine leishmaniosis following vertical transmission in United States dogs

Abstract

Canine leishmaniosis (CanL) is caused by Leishmania infantum, an obligate intracellular protozoan parasite, endemic in U.S. hunting dog populations. CanL has been found in dogs in 28 states and two Canadian provinces. Previous studies by our group, (Boggiatto, 2011), demonstrated that vertical transmission of Leishmania was the predominant means of transmission within U.S. dogs. Very little is known regarding how this alternative means of transmission, alters the long-term immunity and clinical presentation of leishmaniosis in dogs born to a positive bitch. This study follows the immunological progression of CanL in three pups after birth to an infected bitch. During the course of the study, these dogs were tested every six months over the course of six years. Both immunologic (IFN-γ, T cell proliferation, antibody production) and parasitological parameters (qPCR) of vertically-infected dogs were measured. Within the six years after birth to an L. infantum-infected, oligosymptomatic bitch, all dogs had at least one L. infantum PCR-positive test. Interestingly, despite living in the same location for their entire lives and being full siblings, these pups demonstrate three different disease progression patterns of L. infantum infection. One dog progressed to oligosymptomatic disease, maintaining a positive titer and had intermittent positive PCR results. One asymptomatic dog had positive serological titers and demonstrated a robust CD4+ immune response to infection. The third dog had a negligible response to L. infantum antigen and was healthy. This work demonstrates the biologic variability associated with vertically-transmitted infection similar to the variety of presentations observed during vector-borne leishmaniosis.

Leishmania-Derived Trimannose Modulates the Inflammatory Response To Significantly Reduce Leishmania major-Induced Lesions

“…Parasite DNA isolation and qPCR were performed as previously described (43)(44)(45). DNA was isolated from homogenized footpads with a QIAamp DNA blood minikit per the manufacturer's instruction (Qiagen, Valencia, CA).…”

“…DNA was isolated from homogenized footpads with a QIAamp DNA blood minikit per the manufacturer's instruction (Qiagen, Valencia, CA). Ribosomal primer sequences F (5=-AAGCCACCCC AGAGGTAAAAA) and R (5=-GACGGGTCTGACCCTTGGTT) (Invitrogen, Life Technologies, Grand Island, NY) and the probe 5=-FAM-CGGTTCGGTGTGTGGCGCC-MGBNFQ, where FAM is 6-carboxyfluorescein (Applied Biosystems, Life Technologies, Grand Island, NY), were used as previously described (45). The primers and probe were used at 10 nM.…”

“…The primers and probe were used at 10 nM. Amplification was performed in duplicate using an ABI 7900 qPCR system (Applied Biosystems) with Super Mastermix (carboxy-X-rhodamine) (Quanta Biosciences, Gaithersburg, MD) and the cycling protocol described previously (45). The results were analyzed by use of the ABI SDS (version 2.4.1) program (Applied Biosystems).…”

Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis

“…The average age of the study population was 4.1 years old. For more information about the natural history of VL from birth in a subset of these dogs, see Vida et al , 2016 (54). …”

Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant

“…Parasite DNA isolation and qPCR was performed as previously described [29, 30, 34]. DNA was isolated from canine blood samples with the QIAamp DNA Blood Mini Kit per manufacturer’s instruction (QIAGEN, Valencia, CA).…”