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

  • Claudia M. Solt , Jessica L. Hill , Kim Vanderpool and Michelle T. Foster EMAIL logo
Published/Copyright: May 28, 2019

Abstract

Background

Inflammation, 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 methods

Four-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).

Results

Compared 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.

Discussion

Overall, 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.

Funding source: NIDDK

Award Identifier / Grant number: P30DK048520

Funding statement: This study was supported by NIH NIDDK R03DK099425, Funder Id: http://dx.doi.org/10.13039/100000062, Grant Number: P30DK048520.

Author Statement

  1. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest.

  2. Informed consent: Not applicable.

  3. Ethical approval: All experiments were conducted in accordance with the National Institutes of Health Guidelines for the Care and Use of Experimental Animals and were approved by the Colorado State University Institutional Animal Care and Use Committee.

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Received: 2018-12-23
Accepted: 2019-04-01
Published Online: 2019-05-28

©2019 Walter de Gruyter GmbH, Berlin/Boston

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