Roles of neutrophil β2 integrins in kinetics of bacteremia, extravasation, and tick acquisition of Anaplasma phagocytophila in mice

Borjesson, Dori L.; Simon, Scott I.; Hodzic, Emir; DeCock, Hilde E. V.; Ballantyne, Christie M.; Barthold, Stephen W.

doi:10.1182/blood-2002-04-1019

Cited by 19 publications

(22 citation statements)

References 40 publications

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“…In view of these critical functions, leukocyte adhesin deficiencies have been associated with enhanced susceptibility to recurrent infections in human patients (48) and vulnerability to experimental infection in knockout mice. For example, mice lacking CR3 are more susceptible than wild-type littermates to experimental infections with Streptococcus pneumoniae (49) or the tick-borne agent of human granulocytic erlichiosis, Anaplasma phagocytophila (50), and mice treated with anti-CD11b mAb are vulnerable to L. monocytogenes (51). Because phagocytes, both neutrophils and M, are thought to play pivotal roles in innate host immunity to B. dermatitidis, it was unclear whether loss of the leukocyte adhesion receptor CD11b/CD18 (CR3) would disadvantage the host or the pathogen during experimental pulmonary blastomycosis.…”

Section: Discussionmentioning

confidence: 99%

Exploiting Type 3 Complement Receptor for TNF-α Suppression, Immune Evasion, and Progressive Pulmonary Fungal Infection

Brandhorst

Wüthrich

Finkel-Jimenez

et al. 2004

The Journal of Immunology

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TNF-α is crucial in defense against intracellular microbes. Host immune cells use type 3 complement receptors (CR3) to regulate excess TNF-α production during physiological clearance of apoptotic cells. BAD1, a virulence factor of Blastomyces dermatitidis, is displayed on yeast and released during infection. BAD1 binds yeast to macrophages (Mφ) via CR3 and CD14 and suppresses TNF-α, which is required for resistance. We investigated whether blastomyces adhesin 1 (BAD1) exploits host receptors for immune deviation and pathogen survival. Soluble BAD1 rapidly entered Mφ, accumulated intracellularly by 10 min after introduction to cells, and trafficked to early and late endosomes. Inhibition of receptor recycling by monodansyl cadaverine blocked association of BAD1 with Mφ and reversed TNF-α suppression in vitro. Inhibition of BAD1 uptake with cytochalasin D and FcR-redirected delivery of soluble BAD1 as Ag-Ab complexes or of wild-type yeast opsonized with IgG similarly reversed TNF-α suppression. Hence, receptor-mediated entry of BAD1 is requisite in TNF-α suppression, and the route of entry is critical. Binding of soluble BAD1 to Mφ of CR3−/− and CD14−/− mice was reduced to 50 and 33%, respectively, of that in wild-type mice. Mφ of CR3−/− and CD14−/− mice resisted soluble BAD1 TNF-α suppression in vitro, but, in contrast to CR3−/− cells, CD14−/− cells were still subject to suppression mediated by surface BAD1 on wild-type yeast. CR3−/− mice resisted both infection and TNF-α suppression in vivo, in contrast to wild-type and CD14−/− mice. BAD1 of B. dermatitidis thus co-opts normal host cell physiology by exploiting CR3 to subdue TNF-α production and foster pathogen survival.

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Section: Discussionmentioning

confidence: 99%

Exploiting Type 3 Complement Receptor for TNF-α Suppression, Immune Evasion, and Progressive Pulmonary Fungal Infection

Brandhorst

Wüthrich

Finkel-Jimenez

et al. 2004

The Journal of Immunology

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“…Thus, tick infestation was used to document that cytopenias and BM alterations occur in the mouse model using a physiologically relevant route of infection. For tick infestation, C3H mice were infested with A. phagocytophilum-infected or uninfected nymphal Ixodes scapularis ticks exactly as previously described (11). Nymphal I. scapularis ticks were kindly provided by Durland Fish (Yale School of Public Health, New Haven, CT).…”

Section: Mice and In Vivo Experimental Infectionmentioning

confidence: 99%

“…Mouse experiments were performed as previously described (11). Female, 5-to 8-week-old C3H/HeN (C3H) and C3H/Smn.ClcrHsd-scid (SCID) mice were purchased from National Cancer Institute Animal Production Program, Frederick Cancer Research Center (Frederick, MD) and Harlan Sprague-Dawley (Indianapolis, IN), respectively.…”

Section: Mice and In Vivo Experimental Infectionmentioning

confidence: 99%

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Infection withAnaplasma phagocytophilumInduces Multilineage Alterations in Hematopoietic Progenitor Cells and Peripheral Blood Cells

et al. 2009

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Infection withHematopoietic lineage assessment demonstrated that there was loss of erythrocytes and B lymphocytes from the BM along with increased granulopoiesis. These changes were accompanied by splenomegaly due to lymphoid hyperplasia and increased hematopoiesis, most notably erythropoiesis. These changes largely mimic well-described inflammation and endotoxin-mediated effects on the BM and spleen; however, the numbers of peripheral blood neutrophils appear to be independently modulated as granulocytic hyperplasia does not result in neutrophilia. Our findings highlight a well-conserved series of events that we demonstrate can be instigated by an LPS-negative pathogen in the absence of an endotoxin-mediated acute proinflammatory response.

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“…While mice do not consistently develop signs of clinical disease as described in humans, horses, or nonhuman primates, they do develop an acute infection and associated pathologic changes. 1,[7][8][9][10]12,13,15,23,24,31,38,39,42,46 In this study we report the results of a pathologic study of acute A phagocytophilum infection in C3H/HeJ mice and discuss the relative importance and advantages of this mouse model in contrast to other A phagocytophilum models and hosts.…”

mentioning

confidence: 99%

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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Roles of neutrophil β2 integrins in kinetics of bacteremia, extravasation, and tick acquisition of Anaplasma phagocytophila in mice

Cited by 19 publications

References 40 publications

Exploiting Type 3 Complement Receptor for TNF-α Suppression, Immune Evasion, and Progressive Pulmonary Fungal Infection

Exploiting Type 3 Complement Receptor for TNF-α Suppression, Immune Evasion, and Progressive Pulmonary Fungal Infection

Infection withAnaplasma phagocytophilumInduces Multilineage Alterations in Hematopoietic Progenitor Cells and Peripheral Blood Cells

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

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