The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections

Abstract

Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data.

The Immune Response in Adipocytes and Their Susceptibility to Infection: A Possible Relationship with Infectobesity

“…In monocytes, leptin also influences activation, phagocytosis, and cytokine production (TNF-α, IL-1, IL-6, IL-8, and IL-18) and cell proliferation. In turn, leptin expression is also elevated by proinflammatory cytokines such as TNF-α and IL-1, indicating a bidirectional interaction between leptin and inflammation [ 25 , 26 , 27 , 32 ].…”

“…In subjects with increased body masses, the downregulation of adiponectin has been detected, and adiponectin levels have been shown to be inversely correlated with glucose intolerance and type 2 diabetes. In this context, adiponectin appears to promote beta-cell function and survival [ 32 ]. Moreover, adiponectin enhances insulin secretion by stimulating both the expression of the insulin gene and the exocytosis of insulin granules [ 33 ].…”

“…In fact, older ICAM-1-deficient mice, or even those lacking CD11b/CD18 (one of the main ligands for ICAM-1), have shown an increase in obesity [ 37 ]. Additionally, adiponectin levels are decreased in obese and type 2 diabetic subjects and negatively correlate with visceral mass [ 32 ].…”

Autologous human immunocompetent white adipose tissue-on-chip

“…Marked by a state of low-grade chronic inflammation, obesity is a well-recognized risk factor for a myriad of co-morbidities, amongst them type 2 diabetes mellitus (T2DM), cardiovascular and neurodegenerative diseases, at least 13 different types of cancer (National Cancer Institute at the National Institutes of Health, 2020), and infectious diseases [e.g. COVID19 (Andrade et al, 2021;Hornung et al, 2021)]. Moreover, being obese directly impacts the immune system's ability to respond to infections (Alarcon et al, 2021;Hornung et al, 2021).…”

“…COVID19 (Andrade et al, 2021;Hornung et al, 2021)]. Moreover, being obese directly impacts the immune system's ability to respond to infections (Alarcon et al, 2021;Hornung et al, 2021). Therefore, in the era of 'diabesity' and due to its central role for metabolic and endocrine processes, adipose tissue has become a target of high interest for therapeutic strategies against various diseases.…”