scholarly journals Prion strain-dependent tropism is maintained between spleen and granuloma and relies on lymphofollicular structures

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Iman Al-Dybiat ◽  
Mohammed Moudjou ◽  
Davy Martin ◽  
Fabienne Reine ◽  
Laetitia Herzog ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymphoid Tissue ◽  
Detection Method ◽  
Prion Diseases ◽  
Follicular Dendritic Cells ◽  
Prion Strain ◽  
Strain Type ◽  
Lymphoid Structures ◽  
Nonlymphoid Tissue ◽  
Strain Dependent

Abstract In peripherally acquired prion diseases, prions move through several tissues of the infected host, notably in the lymphoid tissue, long before the occurrence of neuroinvasion. Accumulation can even be restricted to the lymphoid tissue without neuroinvasion and clinical disease. Several experimental observations indicated that the presence of differentiated follicular dendritic cells (FDCs) in the lymphoid structures and the strain type are critical determinants of prion extraneural replication. In this context, the report that granulomatous structures apparently devoid of FDCs could support prion replication raised the question of the requirements for prion lymphotropism. The report also raised the possibility that nonlymphoid tissue-tropic prions could actually target these inflammatory structures. To investigate these issues, we examined the capacity of closely related prions, albeit with opposite lymphotropism (or FDC dependency), for establishment in experimentally-induced granuloma in ovine PrP transgenic mice. We found a positive correlation between the prion capacity to accumulate in the lymphoid tissue and granuloma, regardless of the prion detection method used. Surprisingly, we also revealed that the accumulation of prions in granulomas involved lymphoid-like structures associated with the granulomas and containing cells that stain positive for PrP, Mfge-8 but not CD45 that strongly suggest FDCs. These results suggest that the FDC requirement for prion replication in lymphoid/inflammatory tissues may be strain-dependent.

scholarly journals Immunohistochemical antigen demonstration in plastic-embedded lymphoid tissue.

1988 ◽  
Vol 36 (1) ◽  
pp. 115-120 ◽  
Author(s):  
H van Goor ◽  
G Harms ◽  
P O Gerrits ◽  
F G Kroese ◽  
S Poppema ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Monoclonal Antibodies ◽  
Phosphate Buffer ◽  
Lymphoid Tissue ◽  
Common Antigen ◽  
Follicular Dendritic Cells ◽  
Glycol Methacrylate ◽  
Wide Range ◽  
Sucrose Phosphate

We describe a method for post-embedding immunohistochemical demonstration of a wide range of antigens in glycol methacrylate-embedded tissue. Rat spleen and thymus tissues were fixed by immersion in fixatives containing different concentrations of paraformaldehyde, washed in sucrose phosphate buffer, dehydrated in acetone, infiltrated in a glycol methacrylate mixture in which the commonly used softener 2-butoxyethanol was replaced by butaandiol monoacrylate, and embedded. Trypsin was used to re-expose the masked antigenicity. Excellent results were obtained with a panel of monoclonal antibodies (MoAbs) directed against T-cells, B-cells, Ia-positive cells, macrophages, follicular dendritic cells, and leucocyte common antigen-bearing cells. The method described combines exact localization of antigens with optimal tissue morphology.

Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells

2007 ◽  
Vol 129 (3) ◽  
pp. 311-320 ◽  
Author(s):  
Phebe Verbrugghe ◽  
Pekka Kujala ◽  
Wim Waelput ◽  
Peter J. Peters ◽  
Claude A. Cuvelier
Keyword(s):  
Dendritic Cells ◽  
Lymphoid Tissue ◽  
M Cells ◽  
Follicular Dendritic Cells ◽  
Human Gut ◽  
Follicular Dendritic

scholarly journals Induced bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells

2009 ◽  
Vol 206 (12) ◽  
pp. 2593-2601 ◽  
Author(s):  
Stephan Halle ◽  
Hélène C. Dujardin ◽  
Nadja Bakocevic ◽  
Henrike Fleige ◽  
Heike Danzer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Lymphoid Tissue ◽  
Two Photon Microscopy ◽  
Mucosal Vaccination ◽  
Modified Vaccinia Virus Ankara ◽  
Lymphoid Structures ◽  
Underlying Mechanisms

Mucosal vaccination via the respiratory tract can elicit protective immunity in animal infection models, but the underlying mechanisms are still poorly understood. We show that a single intranasal application of the replication-deficient modified vaccinia virus Ankara, which is widely used as a recombinant vaccination vector, results in prominent induction of bronchus-associated lymphoid tissue (BALT). Although initial peribronchiolar infiltrations, characterized by the presence of dendritic cells (DCs) and few lymphocytes, can be found 4 d after virus application, organized lymphoid structures with segregated B and T cell zones are first observed at day 8. After intratracheal application, in vitro–differentiated, antigen-loaded DCs rapidly migrate into preformed BALT and efficiently activate antigen-specific T cells, as revealed by two-photon microscopy. Furthermore, the lung-specific depletion of DCs in mice that express the diphtheria toxin receptor under the control of the CD11c promoter interferes with BALT maintenance. Collectively, these data identify BALT as tertiary lymphoid structures supporting the efficient priming of T cell responses directed against unrelated airborne antigens while crucially requiring DCs for its sustained presence.

scholarly journals Orally Administered Amyloidophilic Compound Is Effective in Prolonging the Incubation Periods of Animals Cerebrally Infected with Prion Diseases in a Prion Strain-Dependent Manner

2007 ◽  
Vol 81 (23) ◽  
pp. 12889-12898 ◽  
Author(s):  
Yuri Kawasaki ◽  
Keiichi Kawagoe ◽  
Chun-jen Chen ◽  
Kenta Teruya ◽  
Yuji Sakasegawa ◽  
...  
Keyword(s):  
Prion Protein ◽  
Therapeutic Efficacy ◽  
Prion Diseases ◽  
Neuroblastoma Cells ◽  
Therapeutic Interventions ◽  
Dependent Manner ◽  
Cell Culture Study ◽  
Prion Strain ◽  
Incubation Periods ◽  
Strain Dependent

ABSTRACT The establishment of effective therapeutic interventions for prion diseases is necessary. We report on a newly developed amyloidophilic compound that displays therapeutic efficacy when administered orally. This compound inhibited abnormal prion protein formation in prion-infected neuroblastoma cells in a prion strain-dependent manner: effectively for RML prion and marginally for 22L prion and Fukuoka-1 prion. When the highest dose (0.2% [wt/wt] in feed) was given orally to cerebrally RML prion-inoculated mice from inoculation until the terminal stage of disease, it extended the incubation periods by 2.3 times compared to the control. The compound exerted therapeutic efficacy in a prion strain-dependent manner such as that observed in the cell culture study: most effective for RML prion, less effective for 22L prion or Fukuoka-1 prion, and marginally effective for 263K prion. Its effectiveness depended on an earlier start of administration. The glycoform pattern of the abnormal prion protein in the treated mice was modified and showed predominance of the diglycosylated form, which resembled that of 263K prion, suggesting that diglycosylated forms of abnormal prion protein might be least sensitive or resistant to the compound. The mechanism of the prion strain-dependent effectiveness needs to be elucidated and managed. Nevertheless, the identification of an orally available amyloidophilic chemical encourages the pursuit of chemotherapy for prion diseases.

scholarly journals Clearance of Chikungunya Virus Infection in Lymphoid Tissues Is Promoted by Treatment with an Agonistic Anti-CD137 Antibody

2019 ◽  
Vol 93 (24) ◽  
Author(s):  
Jun P. Hong ◽  
Mary K. McCarthy ◽  
Bennett J. Davenport ◽  
Thomas E. Morrison ◽  
Michael S. Diamond
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Immune Responses ◽  
Germinal Center ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Follicular Dendritic Cells ◽  
Chikv Infection ◽  
Musculoskeletal Tissues ◽  
Follicular Dendritic

ABSTRACT CD137, a member of the tumor necrosis factor receptor superfamily of cell surface proteins, acts as a costimulatory receptor on T cells, natural killer cells, B cell subsets, and some dendritic cells. Agonistic anti-CD137 monoclonal antibody (MAb) therapy has been combined with other chemotherapeutic agents in human cancer trials. Based on its ability to promote tumor clearance, we hypothesized that anti-CD137 MAb might activate immune responses and resolve chronic viral infections. We evaluated anti-CD137 MAb therapy in a mouse infection model of chikungunya virus (CHIKV), an alphavirus that causes chronic polyarthritis in humans and is associated with reservoirs of CHIKV RNA that are not cleared efficiently by adaptive immune responses. Analysis of viral tropism revealed that CHIKV RNA was present preferentially in splenic B cells and follicular dendritic cells during the persistent phase of infection, and animals lacking B cells did not develop persistent CHIKV infection in lymphoid tissue. Anti-CD137 MAb treatment resulted in T cell-dependent clearance of CHIKV RNA in lymphoid tissue, although this effect was not observed in musculoskeletal tissue. The clearance of CHIKV RNA from lymphoid tissue by anti-CD137 MAb was associated with reductions in the numbers of germinal center B cells and follicular dendritic cells. Similar results were observed with anti-CD137 MAb treatment of mice infected with Mayaro virus, a related arthritogenic alphavirus. Thus, anti-CD137 MAb treatment promotes resolution of chronic alphavirus infection in lymphoid tissues by reducing the numbers of target cells for infection and persistence. IMPORTANCE Although CHIKV causes persistent infection in lymphoid and musculoskeletal tissues in multiple animals, the basis for this is poorly understood, which has hampered pharmacological efforts to promote viral clearance. Here, we evaluated the therapeutic effects on persistent CHIKV infection of an agonistic anti-CD137 MAb that can activate T cell and natural killer cell responses to clear tumors. We show that treatment with anti-CD137 MAb promotes the clearance of persistent alphavirus RNA from lymphoid but not musculoskeletal tissues. This occurs because anti-CD137 MAb-triggered T cells reduce the numbers of target germinal center B cells and follicular dendritic cells, which are the primary reservoirs for CHIKV in the spleen and lymph nodes. Our studies help to elucidate the basis for CHIKV persistence and begin to provide strategies that can clear long-term cellular reservoirs of infection.

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