scholarly journals Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, RT-SHIV RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates

2021 ◽  
Author(s):  
Erin M.B. Scholz ◽  
Joseph N. Mwangi ◽  
Gabriela De la Cruz ◽  
Michael Nekorchuk ◽  
Chi Ngai Chan ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Nonhuman Primates ◽  
Quantitative Imaging ◽  
Viral Rna ◽  
Lymphoid Tissues ◽  
Imaging Analysis ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Tissue Area ◽  
Total Tissue

HIV persistence in tissue reservoirs is a major barrier to HIV cure. While antiretrovirals (ARVs) suppress viral replication, antiretroviral therapy (ART) interruption results in rapid rebound viremia that may originate from lymphoid tissues. To understand the relationship between anatomic distribution of ARV exposure and viral expression in lymph nodes, we performed mass spectrometry imaging (MSI) of 6 ARVs, RNAscope in situ hybridization for viral RNA, and immunohistochemistry of collagen in mesenteric lymph nodes from 8 uninfected and 10 reverse transcriptase-simian/human immunodeficiency virus (RT-SHIV) infected rhesus macaque nonhuman primates (NHPs) dosed to steady-state with combination ART. MATLAB-based quantitative imaging analysis was used to evaluate spatial and pharmacologic relationships between these ARVs, viral RNA (both vRNA+ cells and FDC-bound virions) and collagen deposition. Using MSI, 31% of mesenteric lymph node tissue area was not covered by any ARV. Additionally, 28% of FDC-trapped virions and 21% of infected cells were not exposed to any detected ARV. Of the 69% of tissue area that was covered by cumulative ART exposure, nearly 100% of concentrations were greater than in vitro IC50 values; however, 52% of total tissue coverage was from only one ARV, primarily maraviroc. Collagen covered ∼35% of tissue area, but did not influence ARV distribution heterogeneity. Our findings are consistent with our hypothesis that ARV distribution, in addition to total-tissue drug concentration, must be considered when evaluating viral persistence in lymph nodes and other reservoir tissues.

scholarly journals Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80.

1985 ◽  
Vol 161 (3) ◽  
pp. 475-489 ◽  
Author(s):  
S H Lee ◽  
P M Starkey ◽  
S Gordon
Keyword(s):  
Bone Marrow ◽  
Small Bowel ◽  
Lymph Nodes ◽  
Large Bowel ◽  
Adult Mouse ◽  
Specific Antigen ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Mouse Tissues

We have estimated the macrophage content of different tissues of the normal adult mouse using F4/80, a highly specific antigen marker for mature mouse macrophages. An absorption indirect binding assay was used to quantitate F4/80 antigen against a calibration standard made from the J774.2 macrophage-like cell line. The richest sources of tissue F4/80 antigen were found to be bone marrow, spleen, cervical and mesenteric lymph nodes, large bowel, liver, kidneys, and small bowel. The organs that have the highest total F4/80 antigen content are the liver, large bowel, small bowel, bone marrow, spleen, cervical and mesenteric lymph nodes, and kidney. We conclude that the mononuclear phagocyte system is mainly distributed in the gastrointestinal tract and liver, followed by hemopoietic and lymphoid tissues.

scholarly journals Salmonella TyphimuriumInfection Along the Porcine Gastrointestinal Tract and Associated Lymphoid Tissues

2019 ◽  
Vol 56 (5) ◽  
pp. 681-690 ◽  
Author(s):  
Natividad Bellido-Carreras ◽  
Héctor Argüello ◽  
Sara Zaldívar-López ◽  
Ángeles Jiménez-Marín ◽  
Rodrigo P. Martins ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Control Strategies ◽  
Foodborne Pathogen ◽  
Early Time ◽  
Effective Control ◽  
Lymphoid Tissues ◽  
Polymorphonuclear Cells ◽  
Mesenteric Lymph Nodes ◽  
Time Points ◽  
Mesenteric Lymph

Salmonella is a major foodborne pathogen and pork is one of the main sources of human salmonellosis. Understanding the pathogenesis and progression of the infection within the host is of interest to establish potential approaches to control the disease in pigs. The present study evaluates factors such as intestinal colonization, fecal shedding, and pathogen persistence by 2 studies using experimental challenge with Salmonella Typhimurium in weaned pigs and euthanasia at different time points (1, 2, and 6 and 2, 14, and 30 days postinfection [dpi], respectively). Histopathology of intestine at early time points (1 dpi and 2 dpi) showed severe damage to the epithelium together with an increase in polymorphonuclear cells and macrophages ( P < .001), particularly in jejunum and ileum. Large quantities of Salmonella were detected within the contents of the ileum, cecum, and colon in early infection. Salmonella could also be observed in the medulla of tonsils and mesenteric lymph nodes. From 6 dpi onward, signs of recovery were observed, with progressive restoration of the epithelium, reduction of the inflammatory infiltrate, and elimination of Salmonella from the mucosa. Concentration of Salmonella in feces and ileum content decreased, but shedding did not cease even at 4 weeks after infection. Persistence of the bacteria in mesenteric lymph nodes was identified within the connective tissue at 14 and 30 dpi. Our results demonstrate a recovery of the disease after an initial acute phase but also show persistence within the lumen and surrounding lymphoid tissue. These findings are relevant to developing effective control strategies.

scholarly journals CCR7-dependent trafficking of RORγ+ ILCs creates a unique microenvironment within mucosal draining lymph nodes

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Emma C. Mackley ◽  
Stephanie Houston ◽  
Clare L. Marriott ◽  
Emily E. Halford ◽  
Beth Lucas ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Lymphoid Cells ◽  
Intestinal Cells ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Cell Responses ◽  
Mesenteric Lymph ◽  
Peripheral Lymph ◽  
Group 3 ◽  
Draining Lymph Nodes

Abstract Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control of CD4 T-cell responses to commensal bacteria. It is not known whether ILC populations migrate from their mucosal and peripheral sites to local draining secondary lymphoid tissues. Here we demonstrate that ILC3s reside within the interfollicular areas of mucosal draining lymph nodes, forming a distinct microenvironment not observed in peripheral lymph nodes. By photoconverting intestinal cells in Kaede mice we reveal constitutive trafficking of ILCs from the intestine to the draining mesenteric lymph nodes, which specifically for the LTi-like ILC3s was CCR7-dependent. Thus, ILC populations traffic to draining lymph nodes using different mechanisms.

scholarly journals Intracellular localization and properties of phosphate-dependent glutaminase in rat mesenteric lymph nodes

1984 ◽  
Vol 217 (1) ◽  
pp. 289-296 ◽  
Author(s):  
M S M Ardawi ◽  
E A Newsholme
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Intracellular Localization ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Ph Optimum ◽  
Mesenteric Lymph ◽  
Phosphorylated Compounds ◽  
Glutaminase Activity

Phosphate-dependent glutaminase was present at approximately similar activities in lymph nodes from mammals other than rat, and in thymus, spleen, Peyer's patches and bone marrow of the rat. This suggests that glutamine is important in all lymphoid tissues. Phosphate-dependent glutaminase activity was shown to be present primarily in the mitochondria of rat mesenteric lymph nodes, and most of the activity could be released by detergents. The properties of the enzyme in mitochondrial extracts were investigated. The pH optimum was 8.6 and the Km for glutamine was 2.0 mM. The enzyme was activated by phosphate, other phosphorylated compounds including phosphoenolpyruvate, and also leucine: 50% activation occurred at 5, 0.2 and 0.6 mM for phosphate, phosphoenolpyruvate and leucine respectively. The enzyme was inhibited by glutamate, 2-oxoglutarate, citrate and ammonia, and by N-ethylmaleimide and diazo-5-oxo-L-norleucine; 50% inhibition was observed at 0.7 and 0.1 mM for glutamate and 2-oxoglutarate respectively. Some of these properties may be important in the control of the enzyme activity in vivo.

scholarly journals Detection of Visna Maedi virus in mesenteric lymph nodes and in other lymphoid tissues of sheep three years after respiratory infection

2013 ◽  
Vol 58 (No. 7) ◽  
pp. 359-363 ◽  
Author(s):  
S. Preziuso ◽  
GE Magi ◽  
S. Mari ◽  
G. Renzoni
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Infected Sheep ◽  
Viral Capsid ◽  
Lymphoid Tissues ◽  
Viral Capsid Antigen ◽  
Mesenteric Lymph Nodes ◽  
Proviral Dna ◽  
Mesenteric Lymph ◽  
Target Organs

Visna/Maedi virus (VMV), a small ruminant lentivirus responsible for lymphoproliferative pneumonia, encephalitis, arthritis and/or mastitis in sheep, has been detected in different non-lymphoid organs. However, only a few investigations have been carried out in lymphoid tissues. In this study, some lymphoid tissues and lymph node draining or non-draining VMV target organs from five sheep infected experimentally by the respiratory route three years previously were investigated. Archival samples of spleen, red bone marrow, caudal mediastinal lymph nodes, mammary lymph nodes, popliteal lymph nodes and mesenteric lymph nodes were tested by PCR for the presence of proviral DNA. Popliteal and mesenteric lymph node samples were tested also by immunohistochemical staining of the viral capsid antigen p28. The proviral DNA was detected by PCR in all the lymphoid tissue samples from the infected sheep. The viral antigen was stained in mononuclear cells in popliteal and mesenteric lymph nodes of the infected sheep. Although the lymph nodes draining the classical target organs seem to be more infected than the others, both the viral capsid antigen and the proviral DNA were present also in lymph nodes draining non-target organs, such as the mesenteric lymph nodes. These findings show the presence of VMV in different lymphoid tissues in the late stages of infection and suggest a potential role of these tissues as a site for viral reservoir and replication, even three years after infection. &nbsp;

scholarly journals In situ hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) in vivo

2001 ◽  
Vol 82 (9) ◽  
pp. 2225-2234 ◽  
Author(s):  
Carmen Cantó-Nogués ◽  
Sue Jones ◽  
Rebecca Sangster ◽  
Peter Silvera ◽  
Robin Hull ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Immunodeficiency Virus ◽  
Early Replication ◽  
Dna Pcr

The distribution of virus-infected cells in cynomolgus macaques was determined at 4, 7, 14 and 28 days following intravenous challenge with 1000 TCID50 of the wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point, pairs of macaques were killed humanely and the presence of SIV was determined and quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by in situ hybridization (ISH). At day 4 post-infection (p.i.), detection of the virus was sporadic. By day 7 p.i., however, significant SIV loads were detected in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by ISH and significantly fewer (P<0·05) in the spleen. Significant numbers of ISH-positive cells were also observed in sections of ileum. By day 14 p.i., the distribution of SIV was more even in all lymphoid tissues analysed. By day 28, most of the tissues were negative by ISH, but all remained positive by virus isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with monoclonal antibodies specific for SIV envelope and Nef largely confirmed the observations from ISH. These results indicate that, even following intravenous challenge, a major site of the initial replication of SIV is gut-associated lymphoid tissue. Vaccines that induce protection at this site may therefore be superior, even against parenteral challenge.

scholarly journals Cytokine Response in Multiple Lymphoid Tissues during the Primary Phase of Feline Immunodeficiency Virus Infection

1998 ◽  
Vol 72 (12) ◽  
pp. 9436-9440 ◽  
Author(s):  
Gregg A. Dean ◽  
Niels C. Pedersen
Keyword(s):  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Cytokine Mrna ◽  
Cervical Lymph Nodes ◽  
Mesenteric Lymph ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-γ). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-γ, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-γ, IL-12p40 and IL-10. An increase in IFN-γ, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4+ cells were the primary source of IL-2, IL-4, and IL-10. Both CD4+ and CD8+ cells produced IFN-γ, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.

Early lymphocytic responses to Heligmosomoides polygyrus infections in mice

1990 ◽  
Vol 64 (1) ◽  
pp. 35-45 ◽  
Author(s):  
S. J. Parker ◽  
C. J. Inchley
Keyword(s):  
Lymph Nodes ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Heligmosomoides Polygyrus ◽  
Intestinal Nematode ◽  
Mesenteric Lymph ◽  
Low Responder ◽  
Proliferating Cell ◽  
Draining Lymph Nodes

ABSTRACTResponses to parasite antigens were studied in three strains of mice, BALB/c, CBA and NIH, during the initial phases of a primary infection with the intestinal nematode Heligmosomoides polygyrus. Changes in the rate of in vivo cell division were analysed in mesenteric lymph nodes and spleens during the phases of larval maturation and adult establishment, and related to changes in organ size and cellularity. The nature of the proliferating cell populations was also investigated by flow cytometry, carried out on cell suspensions prepared at the time when larval development was complete. The variation in the ability of the strains of mice to become resistant to a challenge infection was manifest as only slight differences in their initial responses to infection. All three strains showed an increase in 125I-iododeoxyuridine incorporation in their mesenteric lymph nodes and spleen, and an increase in B cell frequency over that of T cells in the draining lymph nodes. Although lymph node weight in NIH mice continued to rise over a 4 week period, the majority of responses measured were short lived, peaking 10 to 14 days after infection. The low responder status of CBA mice was thus reflected in a transient and relatively small enlargement of lymphoid tissues, but their early proliferative responses to antigen were similar in scale to those of responder strains.

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