Obesity-induced immune dysfunction and immunosuppression: TEM observation of visceral and subcutaneous lymph node microarchitecture and immune cell interactions

AbstractBackgroundInflammation, induced by excessive adiposity, links obesity to disease risk yet little attention has been devoted to the lymphoid tissues embedded within adipose tissue depots. Lymph nodes are the primary site for the development of protective immunity, hence any disease process that affects these tissues will also directly impact immunity. Here we examined how obesity alters secondary lymphatic tissue structure and encapsulated immune cells.Materials and methodsFour-month-old C57BL/6 male mice were fed standard rodent chow or a Western high fat diet (HFD) for 6 months. Center regions of visceral and subcutaneous lymph nodes (SQLNS) were observed via transmission electron microscopy (TEM).ResultsCompared with chow, HFD-induced obesity deleteriously modified the structural microarchitecture and immune cell morphology of visceral and SQLNs. In HFD mice, fibroblastic reticular cells (FRCs) were dysregulated while laying among excessive amounts of disorganized collagen (C). In addition HFD lymph nodes contained a disproportionate amount of cellular debris from damaged or dead cells, increased sinus spacing and decreased immune cell interactions. Specifically, dendritic cells (DCs) that are necessary for adaptive immune response where embedded among extracellular debris with decreased pseudopodia. Similarly, the extraneous fibrous extracellular matrix (ECM) in HFD mice limited contact between lymphocytes (LCs) causing their microvilli extensions to decrease.DiscussionOverall, excessive C production within lymph nodes, driven by diet-induced obesity, creates a physical barrier that impedes proper lymph flow and cellular communication. Obesity-induced disorganization of the immune cell guidance network interrupts immune cell adhesion and consequently inhibits travel within cortex regions needed for cell interactions, survival and proliferation.

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Faculty Opinions recommendation of Dynamic imaging of T cell-dendritic cell interactions in lymph nodes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007113.92756 ◽

2002 ◽

Author(s):

Casey Weaver

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Lymph Nodes ◽

Dynamic Imaging ◽

Cell Interactions

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Faculty Opinions recommendation of Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726911501.793526326 ◽

2016 ◽

Author(s):

Cosima Tatiana Baldari ◽

Laura Patrussi

Keyword(s):

Immune Response ◽

Lymph Nodes ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Adrenergic Control ◽

Lymphocyte Recirculation

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Accurate and Robust Alignment of Differently Stained Histologic Images Based on Greedy Diffeomorphic Registration

Applied Sciences ◽

10.3390/app11041892 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1892

Author(s):

Ludovic Venet ◽

Sarthak Pati ◽

Michael D. Feldman ◽

MacLean P. Nasrallah ◽

Paul Yushkevich ◽

...

Keyword(s):

Immune Cell ◽

Tissue Sample ◽

Disease Process ◽

Spatial Arrangement ◽

General Purpose ◽

Growth Patterns ◽

Histological Image ◽

Target Registration Error ◽

Diffeomorphic Registration ◽

3D Information

Histopathologic assessment routinely provides rich microscopic information about tissue structure and disease process. However, the sections used are very thin, and essentially capture only 2D representations of a certain tissue sample. Accurate and robust alignment of sequentially cut 2D slices should contribute to more comprehensive assessment accounting for surrounding 3D information. Towards this end, we here propose a two-step diffeomorphic registration approach that aligns differently stained histology slides to each other, starting with an initial affine step followed by estimating a deformation field. It was quantitatively evaluated on ample (n = 481) and diverse data from the automatic non-rigid histological image registration challenge, where it was awarded the second rank. The obtained results demonstrate the ability of the proposed approach to robustly (average robustness = 0.9898) and accurately (average relative target registration error = 0.2%) align differently stained histology slices of various anatomical sites while maintaining reasonable computational efficiency (<1 min per registration). The method was developed by adapting a general-purpose registration algorithm designed for 3D radiographic scans and achieved consistently accurate results for aligning high-resolution 2D histologic images. Accurate alignment of histologic images can contribute to a better understanding of the spatial arrangement and growth patterns of cells, vessels, matrix, nerves, and immune cell interactions.

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Differentiation of human pluripotent stem cells to brain microvascular endothelial cell-like cells suitable to study immune cell interactions

STAR Protocols ◽

10.1016/j.xpro.2021.100563 ◽

2021 ◽

Vol 2 (2) ◽

pp. 100563

Author(s):

Hideaki Nishihara ◽

Benjamin D. Gastfriend ◽

Pelin Kasap ◽

Sean P. Palecek ◽

Eric V. Shusta ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cell ◽

Pluripotent Stem Cells ◽

Immune Cell ◽

Human Pluripotent Stem Cells ◽

Cell Interactions ◽

Microvascular Endothelial Cell ◽

Brain Microvascular Endothelial Cell ◽

Microvascular Endothelial

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Mast cell–derived particles deliver peripheral signals to remote lymph nodes

Journal of Experimental Medicine ◽

10.1084/jem.20090805 ◽

2009 ◽

Vol 206 (11) ◽

pp. 2455-2467 ◽

Cited By ~ 115

Author(s):

Christian A. Kunder ◽

Ashley L. St. John ◽

Guojie Li ◽

Kam W. Leong ◽

Brent Berwin ◽

...

Keyword(s):

Drug Delivery ◽

Mast Cell ◽

Mast Cells ◽

Tumor Necrosis Factor ◽

Lymph Nodes ◽

Tumor Necrosis ◽

Lymphatic Vessels ◽

Lymphoid Tissues ◽

Draining Lymph Nodes ◽

Necrosis Factor

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.

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

Journal of Experimental Medicine ◽

10.1084/jem.161.3.475 ◽

1985 ◽

Vol 161 (3) ◽

pp. 475-489 ◽

Cited By ~ 254

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.

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HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes

Nature Reviews Immunology ◽

10.1038/nri3298 ◽

2012 ◽

Vol 12 (11) ◽

pp. 762-773 ◽

Cited By ~ 327

Author(s):

Jean-Philippe Girard ◽

Christine Moussion ◽

Reinhold Förster

Keyword(s):

Lymph Nodes ◽

Immune Cell ◽

Cell Trafficking ◽

Immune Cell Trafficking

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The role of gut-associated lymphoid tissues and mucosal defence

British Journal Of Nutrition ◽

10.1079/bjn20041356 ◽

2005 ◽

Vol 93 (S1) ◽

pp. S41-S48 ◽

Cited By ~ 169

Author(s):

Maria Luisa Forchielli ◽

W. Allan Walker

Keyword(s):

Immune System ◽

Breast Milk ◽

Gastrointestinal Disease ◽

Bacterial Colonization ◽

Adaptive Immune Response ◽

Atopic Disease ◽

Mucosal Immune System ◽

Bacterial Invasion ◽

Lymphoid Tissues ◽

Protective Function

The newborn infant leaves a germ-free intrauterine environment to enter a contaminated extrauterine world and must have adequate intestinal defences to prevent the expression of clinical gastrointestinal disease states. Although the intestinal mucosal immune system is fully developed after a full-term birth, the actual protective function of the gut requires the microbial stimulation of initial bacterial colonization. Breast milk contains prebiotic oligosaccharides, like inulin-type fructans, which are not digested in the small intestine but enter the colon as intact large carbohydrates that are then fermented by the resident bacteria to produce SCFA. The nature of this fermentation and the consequent pH of the intestinal contents dictate proliferation of specific resident bacteria. For example, breast milk-fed infants with prebiotics present in breast milk produce an increased proliferation of bifidobacteria and lactobacilli (probiotics), whereas formula-fed infants produce more enterococci and enterobacteria. Probiotics, stimulated by prebiotic fermentation, are important to the development and sustainment of intestinal defences. For example, probiotics can stimulate the synthesis and secretion of polymeric IgA, the antibody that coats and protects mucosal surfaces against harmful bacterial invasion. In addition, appropriate colonization with probiotics helps to produce a balanced T helper cell response (Th1 = Th2 = Th3/Tr1) and prevent an imbalance (Th1 > Th2 or Th2 > Th1) contributing in part to clinical disease (Th2 imbalance contributes to atopic disease and Th1 imbalance contributes to Crohn's disease andHelicobacter pylori-induced gastritis). Furthermore, a series of pattern recognition receptors, toll-like receptors on gut lymphoid and epithelial cells that interact with bacterial molecular patterns (e.g. endotoxin (lipopolysaccharide), flagellin, etc.), help modulate intestinal innate immunity and an appropriate adaptive immune response. Animal and clinical studies have shown that inulin-type fructans will stimulate an increase in probiotics (commensal bacteria) and these bacteria have been shown to modulate the development and persistence of appropriate mucosal immune responses. However, additional studies are needed to show that prebiotics can directly or indirectly stimulate intestinal host defences. If this can be demonstrated, then prebiotics can be used as a dietary supplement to stimulate a balanced and an appropriately effective mucosal immune system in newborns and infants.

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