<i>Treponema pallidum</i>Elicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow‐Cytometric Analysis

Salazar, Juan C.; Cruz, Adriana R.; Pope, Constance D.; Valderrama, Liliana; Trujillo, Rodolfo; Saravia, Nancy Gore; Radolf, Justin D.

doi:10.1086/511822

Cited by 73 publications

(55 citation statements)

References 44 publications

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“…6. Cytokine production by DC exposed to live (LV) or heat-killed (HK) H. ducreyi and LPS singly or in combination after 48 h. Culture supernatants were obtained from DC whose activation levels are reported in Table 1 pallidum have similar proportions of myeloid and plasmacytoid DC in skin lesions and peripheral blood (30,31). The basis for these findings is unclear but could reflect basic differences among these bacteria, such as the lack of LPS in spirochetes, the relative chronicity of each infection, and the inability of H. ducreyi to disseminate systemically.…”

Section: Discussionmentioning

confidence: 99%

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells

Banks¹,

Humphreys²,

Li³

et al. 2007

Infect Immun

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Section: Discussionmentioning

confidence: 99%

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells

Banks¹,

Humphreys²,

Li³

et al. 2007

Infect Immun

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“…To inhibit phagocytosis, cell suspensions were preincubated for 1 h without or with 10 g/ml cytochalasin D (Sigma) prior to the addition of spirochetes and an additional 8 h of incubation. PBMCs were stimulated with live T. pallidum in the presence or absence of 10% heat-inactivated (56°C for 30 min) human syphilitic serum pooled from five human immunodeficiency virus-seronegative donors (99). In some experiments, spirochetes remaining in culture supernatants at the conclusion of the 8-h incubation period were enumerated by dark-field microscopy.…”

Section: Methodsmentioning

confidence: 99%

Phagocytosis ofBorrelia burgdorferi, the Lyme Disease Spirochete, Potentiates Innate Immune Activation and Induces Apoptosis in Human Monocytes

Cruz¹,

Moore²,

Vake³

et al. 2008

Infect Immun

106

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We have previously demonstrated that phagocytosed Borrelia burgdorferi induces activation programs in human peripheral blood mononuclear cells that differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report that ingested B. burgdorferi induces significantly greater transcription of proinflammatory cytokine genes than do lysates and that live B. burgdorferi, but not B. burgdorferi lysate, is avidly internalized by monocytes, where the bacteria are completely degraded within phagolysosomes. In the course of these experiments, we discovered that live B. burgdorferi also induced a dose-dependent decrease in monocytes but not a decrease in dendritic cells or T cells and that the monocyte population displayed morphological and biochemical hallmarks of apoptosis. Particularly noteworthy was the finding that apoptotic changes occurred predominantly in monocytes that had internalized spirochetes. Abrogation of phagocytosis with cytochalasin D prevented the death response. Heat-killed B. burgdorferi, which was internalized as well as live organisms, induced a similar degree of apoptosis of monocytes but markedly less cytokine production. Surprisingly, opsonophagocytosis of Treponema pallidum did not elicit a discernible cell death response. Our combined results demonstrate that B. burgdorferi confined to phagolysosomes is a potent inducer of cytosolic signals that result in (i) production of NF-B-dependent cytokines, (ii) assembly of the inflammasome and activation of caspase-1, and (iii) induction of programmed cell death. We propose that inflammation and apoptosis represent mutually reinforcing components of the immunologic arsenal that the host mobilizes to defend itself against infection with Lyme disease spirochetes.

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“…Exposure to whole T. pallidum and its lipoprotein TpN47 can induce expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin (25,31), which are important in adhesion of immune cells to vascular endothelium for migration into sites of infected tissue. Patients with secondary syphilis have a local immune response in the skin, consisting of monocytes, macrophages, CD4 + and CD8 + T cells, and DCs (32)(33)(34). This proinflammatory response is due to the lipid moiety contained on the many lipoproteins of T. pallidum (35,36).…”

Section: The Natural History Of Syphilis Primary Syphilis -Transmissimentioning

confidence: 99%

“…In addition, the influx of immune cells to syphilis lesions increases the number of cellular targets available for HIV infection and the proximity of HIV-infected cells to transmit virus to the partner. T. pallidum itself and T. pallidum lipoproteins increase the expression of CCR5, the chemokine receptor expressed on macrophages and DCs that acts as a coreceptor for HIV entry into CD4 + cells (33,97).…”

Section: Hiv and Syphilismentioning

confidence: 99%

Syphilis: using modern approaches to understand an old disease

Lukehart²

2011

J. Clin. Invest.

201

168

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Syphilis is a fascinating and perplexing infection, with protean clinical manifestations and both diagnostic and management ambiguities. Treponema pallidum subsp. pallidum, the agent of syphilis, is challenging to study in part because it cannot be cultured or genetically manipulated. Here, we review recent progress in the application of modern molecular techniques to understanding the biological basis of this multistage disease and to the development of new tools for diagnosis, for predicting efficacy of treatment with alternative antibiotics, and for studying the transmission of infection through population networks.

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Treponema pallidumElicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow‐Cytometric Analysis

Abstract: During secondary syphilis, T. pallidum simultaneously elicits local and systemic innate and adaptive immune responses that may set the stage for the bidirectional transmission of HIV.

Cited by 73 publications

References 44 publications

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells

Phagocytosis ofBorrelia burgdorferi, the Lyme Disease Spirochete, Potentiates Innate Immune Activation and Induces Apoptosis in Human Monocytes

Syphilis: using modern approaches to understand an old disease

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