Pathology, Immunohistology, and Cytokine Responses in Early Phases of Human Granulocytic Ehrlichiosis in a Murine Model

Martin, Mary Ellen; Bunnell, Joseph E.; Dumler, J. Stephen

doi:10.1086/315206

Cited by 74 publications

(106 citation statements)

References 14 publications

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“…13,30,44,47,48 In one study, a mild interstitial pneumonia, but with no associated vascular lesions, was described in the C3H/HeJ mouse. 38 In contrast to the human disease and to other studies using the immunocompetent, LPS-responsive, C3H/HeNCr mice, the finding of significant monocytosis by day 10 P.I. appears to be unique in the C3H/HeJ mice.…”

Section: Discussionmentioning

confidence: 62%

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Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of Anaplasma phagocytophilum

et al. 2007

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Abstract. Human granulocytic anaplasmosis (HGA), an emerging disease of public health concern in many areas of the world, is caused by Anaplasma phagocytophilum. Small animal models of A phagocytophilum in laboratory mice have been developed and used to study the pathogenesis of HGA. In this study, we characterized the pathologic changes in acute infection of C3H/HeJ mice experimentally infected with the NY18 isolate of A phagocytophilum. Although no clinical signs were noted, acute infection was associated with gross splenomegaly, microscopic inflammatory lesions in the lung and liver, hyperplastic lesions on the spleen, and clinical pathology abnormalities including neutropenia and monocytosis. This study emphasizes the use of well-defined animal models as a valuable tool for the study of A phagocytophilum infections.

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Section: Discussionmentioning

confidence: 62%

“…13,30,38,46 Microscopically, lesions were present in the spleen, lung, and liver. An apparent neutropenia, monocytosis, and intracytoplasmic morulae in neutrophils, characteristic of A phagocytophilum infection, were also seen.…”

Section: Discussionmentioning

confidence: 99%

Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of Anaplasma phagocytophilum

et al. 2007

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“…Comparison of A. phagocytophilum infection kinetics in several immunocompetent mouse strains has shown that infection is almost undetectable at days 1-2, peaks at day 4 -7, and then rapidly declines at days 8 -10, with some slight variations in C3H/HeN, C3H/HeJ, C57BL/6, BALB/c, DBA/2, and CD1 mice (5,(23)(24)(25)(26)(27)(28)(29)(30). IL-18 secretion kinetics followed a similar pattern in the wild-type mice (Fig.…”

Section: Il-18-null Mice Have Ifn-␥ Impairment and Are Susceptible Tomentioning

confidence: 77%

ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection

Pedra

Sutterwala

Sukumaran

et al. 2007

The Journal of Immunology

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Anaplasma phagocytophilum is an obligate intracellular pathogen that resides within neutrophils and can cause fever, pancytopenia, or death. IFN-γ plays a critical role in the control of A. phagocytophilum; however, the mechanisms that regulate IFN-γ production remain unclear. In this study, we demonstrate that apoptotic specklike protein with a caspase-activating recruiting domain (ASC)/PYCARD, a central adaptor molecule in the Nod-like receptor (NLR) pathway, regulates the IL-18/IFN-γ axis during A. phagocytophilum infection through its effect on caspase-1. Caspase-1- and asc-null mice were more susceptible than control animals to A. phagocytophilum infection due to the absence of IL-18 secretion and reduced IFN-γ levels in the peripheral blood. Moreover, caspase-1 and ASC deficiency reduced CD4+ T cell-mediated IFN-γ after in vitro restimulation with A. phagocytophilum. The NLR family member IPAF/NLRC4, but not NALP3/NLRP3, was partially required for IFN-γ production in response to A. phagocytophilum. Taken together, our data demonstrate that ASC and caspase-1 are critical for IFN-γ-mediated control of A. phagocytophilum infection.

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“…One possible reason for this difference could be that the A. phagocytophila variant 2 is better equipped to elude the immune system by inhibiting antibody response, resulting in more proliferation within granulocytes. This theory is supported by the observation in mice that pathology due to host immunity seems to play a more important role than pathogenicity of Anaplasma itself during infection with HGE (14). However, the role of host immunity in the pathogenesis of TBF in sheep has to be elucidated.…”

Section: Discussionmentioning

confidence: 98%

Identification ofAnaplasma phagocytophila(FormerlyEhrlichia phagocytophila) Variants in Blood from Sheep in Norway

Stuen

Pol²,

Bergström

et al. 2002

J Clin Microbiol

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A total of 41 blood samples were collected from 40 Anaplasma phagocytophila-infected sheep in 11 sheep flocks from four different counties of southern Norway. The presence and nature of the Anaplasma species were identified by microscopic detection of morulae, PCR, reverse line blot hybridization, and 16S rRNA gene sequencing. A. phagocytophila was identified in all of the samples, and sequencing of the 16S rRNA gene revealed the presence of four variants of A. phagocytophila. Two of these variants have been described before, but two were newly identified 16S rRNA variants of this species. A. phagocytophila variant 1 was found in nine flocks, A. phagocytophila variant 2 was found in four flocks, the A. phagocytophila prototype was found in two flocks, and A. phagocytophila variant 5 was found in one flock. In two flocks, some sheep were infected with A. phagocytophila variant 1, whereas others were infected with A. phagocytophila variant 2, and in three animals a double infection with two variants was registered. Analyses of the blood samples revealed that blood from sheep infected with A. phagocytophila variant 2 contained nearly twice as many neutrophils and eight times as many Anaplasma-infected neutrophils as blood from sheep infected with the A. phagocytophila variant 1. Furthermore, only 43% of the A. phagocytophila variant 2-infected sheep displayed antibody responses in an immune fluorescence assay, whereas 93% of the sheep with the A. phagocytophila variant 1-infected sheep were seropositive.

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Pathology, Immunohistology, and Cytokine Responses in Early Phases of Human Granulocytic Ehrlichiosis in a Murine Model

Cited by 74 publications

References 14 publications

Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of Anaplasma phagocytophilum

Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of Anaplasma phagocytophilum

ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection

Identification ofAnaplasma phagocytophila(FormerlyEhrlichia phagocytophila) Variants in Blood from Sheep in Norway

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