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

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.

Characterizing Lymphangiogenesis and Concurrent Inflammation in Adipose Tissue in Response to VEGF-D

“…While a significant increase in B cell recruitment was previously identified in Adipo-VD adipose (Chakraborty et al, 2019), we failed to identify any co-localization of larger number of B220+ cells with new lymphatic structures by immunofluorescence (not shown); increased B cells may still play a role in the tissue. Obesity also reduces lymph node tissue structure, which may be prevented with lymphangiogenic signaling in Adipo-VD mice (Solt et al, 2019). Our study and others' demonstrate that elevated VEGF-D is likely chemotactic toward pro-inflammatory cells, but chronic overexpression in Adipo-VD mice reduces immune accumulation through several potential mechanisms.…”

Changes in the Expression of Insulin Pathway, Neutrophil Elastase and Alpha 1 Antitrypsin Genes from Leukocytes of Young Individuals with Insulin Resistance

“… 52 However, a trend toward decreased IRS-2 expression was observed in both the IR and OB-IR groups that may be related to the presence of insulin resistance, probably associated with chronic low-grade inflammation and immune cell dysfunction in obesity conditions. 53 , 54 …”

Clinical characteristics and outcomes of patients with COVID-19 and ARDS admitted to a third level health institution in Mexico City

“…4. There is an experimental evidence of a compromise in innate and adaptive immunities owing to obesity 34 . In this context, obesity is a public health problem that may be associated with mortality during this pandemic.…”