Obesity Exacerbates the Cytokine Storm Elicited by Francisella tularensis Infection of Females and Is Associated with Increased Mortality

Abstract

Infection with Francisella tularensis, the causative agent of the human disease tularemia, results in the overproduction of inflammatory cytokines, termed the cytokine storm. Excess metabolic byproducts of obesity accumulate in obese individuals and activate the same inflammatory signaling pathways as F. tularensis infection. In addition, elevated levels of leptin in obese individuals also increase inflammation. Since leptin is produced by adipocytes, we hypothesized that increased fat of obese females may make them more susceptible to F. tularensis infection compared with lean individuals. Lean and obese female mice were infected with F. tularensis and the immunopathology and susceptibility monitored. Plasma and tissue cytokines were analyzed by multiplex ELISA and real-time RT-PCR, respectively. Obese mice were more sensitive to infection, developing a more intense cytokine storm, which was associated with increased death of obese mice compared with lean mice. This enhanced inflammatory response correlated with in vitro bacteria-infected macrophage cultures where addition of leptin led to increased production of inflammatory cytokines. We conclude that increased basal leptin expression in obese individuals causes a persistent low-level inflammatory response making them more susceptible to F. tularensis infection and heightening the generation of the immunopathological cytokine storm.

Exploratory examination of inflammation state, immune response and blood cell composition in a human obese cohort to identify potential markers predicting cancer risk

“…This is in contrast to our initial expectation that obese people would have a dampened immune response to bacterial and viral infection, since obesity is a risk factor for infections [2]. However, our finding is consistent with previous studies demonstrating an exaggerated inflammatory response in obese mice infected with bacteria or viruses [51][52][53]. Both the elevated basal and elevated HSV-1-stimulated levels of VEGF, the latter provoking a T H 1 response like a nascent tumor cell, might enable a growing solid tumor, which typically becomes hypoxic, to survive by stimulating blood vessel infiltration into the tumor.…”

Impacts of the COVID-19 Pandemic on Food Security and Diet-Related Lifestyle Behaviors: An Analytical Study of Google Trends-Based Query Volumes

“…Obesity is regarded as a preexisting disease associated with COVID-19 mortality [ 17 ], disease complications, and severe symptoms [ 18 , 19 ]. Obesity is a state of low-grade inflammation, and coronavirus infection may further increase pro-inflammatory cytokine release and oxidative stress leading to exacerbation of a “cytokine storm” [ 20 ]. Vitamins (A, C, D, and E) exert anti-inflammatory or antioxidative effects, which may prevent a virus-induced cytokine storm and prevent tissue damage.…”

Comorbidity Networks in Cardiovascular Diseases

“…Although less evident, the physiological relationship between obesity (in particular its inflammatory component) and critical disorders of the lung is not unknown (Bassetti et al, 2011 ; Pabon et al, 2016 ; Peters et al, 2018 ; Szylińska et al, 2018 ). Under certain circumstances, abnormal immune signals associated with metabolic deregulation may lead to inflammatory proliferation and cytokine storms (Ramos Muniz et al, 2018 ) that may in turn prove critical for certain functions involved in the lung disease (Lee et al, 2016 ).…”