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  1. Article ; Online: Transplacental transmission of Leishmania infantum as a means for continued disease incidence in North America.

    Boggiatto, Paola Mercedes / Gibson-Corley, Katherine Nicole / Metz, Kyle / Gallup, Jack Michael / Hostetter, Jesse Michael / Mullin, Kathleen / Petersen, Christine Anne

    PLoS neglected tropical diseases

    2011  Volume 5, Issue 4, Page(s) e1019

    Abstract: Background: 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- ... ...

    Abstract Background: 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.
    Aims: 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.
    Methodology: 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.
    Key results: 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.
    Major conclusions: 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.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; Cell Proliferation ; DNA, Protozoan/genetics ; DNA, Protozoan/isolation & purification ; Dog Diseases/epidemiology ; Dog Diseases/transmission ; Dogs ; Female ; Infectious Disease Transmission, Vertical ; Leishmania infantum/genetics ; Leishmania infantum/immunology ; Leishmania infantum/isolation & purification ; Leishmaniasis, Visceral/epidemiology ; Leishmaniasis, Visceral/transmission ; Leishmaniasis, Visceral/veterinary ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology ; Pregnancy Complications, Infectious/veterinary ; United States/epidemiology
    Chemical Substances DNA, Protozoan
    Language English
    Publishing date 2011-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0001019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Altered dendritic cell phenotype in response to Leishmania amazonensis amastigote infection is mediated by MAP kinase, ERK.

    Boggiatto, Paola Mercedes / Jie, Fei / Ghosh, Mousumi / Gibson-Corley, Katherine Nicole / Ramer-Tait, Amanda Ellen / Jones, Douglas Elliot / Petersen, Christine Anne

    The American journal of pathology

    2009  Volume 174, Issue 5, Page(s) 1818–1826

    Abstract: Initiation of productive immune responses against Leishmania depends on the successful transition of dendritic cells (DC) from an immature to a mature phenotype. This process is characterized by high CD40 surface expression as well as interleukin-12 ... ...

    Abstract Initiation of productive immune responses against Leishmania depends on the successful transition of dendritic cells (DC) from an immature to a mature phenotype. This process is characterized by high CD40 surface expression as well as interleukin-12 production, which are frequently seen in response to L. major infection. In vivo footpad infection of C3HeB/FeJ mice for 7 days with L. amazonensis promoted an immature CD11c(+) DC phenotype characterized by both significantly low CD40 surface expression and significantly decreased interleukin-12p40 production compared with L. major infection of these same mice. In vitro infection of bone marrow-derived dendritic cells with L. amazonensis amastigotes resulted in rapid and significant phosphorylation of the mitogen activated protein kinase, extracellular signal-regulated kinase 1/2, observed within minutes of exposure to the parasite. Infection with L. amazonensis promastigotes led to increased 1/2 phosphorylation after 4 hours of infection compared with L. major infection, which correlated with promastigote transformation into amastigotes. Treatment of bone marrow-derived dendritic cells with a mitogen activated protein kinase kinase-specific inhibitor, PD98059, led to regained surface CD40 expression and interleukin-12p40 production following L. amazonensis amastigote infection compared with non-treated, infected DC. Treatment of L. amazonensis-infected mice with the highly-specific mitogen activated protein kinase kinase inhibitor, CI-1040, enhanced surface CD40 expression on CD11c(+) DC obtained from the draining lymph node. L. amazonensis amastigotes, through activation of extracellular signal-regulated kinase 1/2, inhibit the ability of DC to undergo proper maturation both in vitro and in vivo.
    MeSH term(s) Animals ; Bone Marrow/metabolism ; Bone Marrow/pathology ; CD11c Antigen/metabolism ; CD40 Antigens/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/parasitology ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Fluorescent Antibody Technique, Indirect ; Host-Parasite Interactions ; Immunoblotting ; Leishmania/immunology ; Mice ; Mice, Inbred C3H ; Mice, SCID ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Phenotype ; Phosphorylation
    Chemical Substances CD11c Antigen ; CD40 Antigens ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2009-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.2353/ajpath.2009.080905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Pathogen-derived oligosaccharides improve innate immune response to intracellular parasite infection.

    Osanya, Alex / Song, Eun-Ho / Metz, Kyle / Shimak, Raeann M / Boggiatto, Paola Mercedes / Huffman, Elise / Johnson, Charles / Hostetter, Jesse M / Pohl, Nicola L B / Petersen, Christine A

    The American journal of pathology

    2011  Volume 179, Issue 3, Page(s) 1329–1337

    Abstract: Pathogen glycolipids, including Leishmania spp. lipophosphoglycan (LPG) and Mycobacterium tuberculosis mannosylated lipoarabinomannan (ManLAM), modulate essential interactions with host phagocytic cells. Polysaccharide and lipid components promote ... ...

    Abstract Pathogen glycolipids, including Leishmania spp. lipophosphoglycan (LPG) and Mycobacterium tuberculosis mannosylated lipoarabinomannan (ManLAM), modulate essential interactions with host phagocytic cells. Polysaccharide and lipid components promote immunomodulation. Owing to the stereochemistry required to synthesize oligosaccharides, the roles for oligosaccharides in the pathogenesis of infectious diseases have remained largely unknown. Recent advances in carbohydrate chemistry allowed us to synthesize pathogen surface oligosaccharides to discern their immune response-altering activities. Trimannose cap carbohydrates from ManLAM and LPG altered the production of proinflammatory cytokines via a toll-like receptor (TLR2)-mediated mechanism in vitro and in vivo. In vivo treatment with trimannose led to increased Th1-polarizing, IL-12p40-producing cells from the draining lymph nodes of treated Leishmania major-infected mice compared with cells from untreated infected mice. Trimannose treatment increased the production of other Th1 proinflammatory cytokines (ie, interferon-γ, IL-6, and tumor necrosis factor-α) critical for a productive immune response to either pathogen. This significant difference in cytokine production between trimannose cap sugar-treated and control groups was not observed in draining lymph node cells from TLR2(-/-) mice. Type of inflammation and rate of bead entry into macrophages and dendritic cells were different for trimannose-coated beads compared with control oligosaccharide-coated beads, indicating selective lectin receptor/oligosaccharide interactions mediating cell entry and cytokine production. These novel findings may prompt the development of targeted oligosaccharide adjuvants against chronic infections.
    MeSH term(s) Animals ; Cell Line ; Cytokines/biosynthesis ; Enzyme-Linked Immunosorbent Assay ; Immunity, Innate/drug effects ; Interleukin-12/metabolism ; Leishmania major/immunology ; Leishmaniasis/immunology ; Leishmaniasis, Cutaneous/immunology ; Macrophages/immunology ; Macrophages/parasitology ; Mice ; Microspheres ; Mycobacterium/immunology ; Oligosaccharides/pharmacology ; Toll-Like Receptor 2/metabolism
    Chemical Substances Cytokines ; Oligosaccharides ; Toll-Like Receptor 2 ; Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2011-07-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2011.05.053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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