The Systemic and Cellular Metabolic Phenotype of Infection and Immune Response to Listeria monocytogenes

Johnson, Robert M.; Olatunde, Adesola; Woodie, Lauren N.; Greene, Michael W.; Schwartz, Elizabeth Hiltbold

doi:10.3389/fimmu.2020.614697

Cited by 4 publications

(3 citation statements)

References 72 publications

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“…The consequences of this change in diet also extended to systemic immune responses, as mice switched to FD could not efficiently clear systemic infections caused by Listeria monocytogenes , a known inducer of type I immune responses 22 (Fig. 1h–j ).…”

Section: Resultsmentioning

confidence: 99%

Short-term dietary changes can result in mucosal and systemic immune depression

Siracusa,

Schaltenberg,

Kumar

et al. 2023

Nat Immunol

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Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to ‘feast diets’, mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4+ T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.

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Section: Resultsmentioning

confidence: 99%

Short-term dietary changes can result in mucosal and systemic immune depression

Siracusa,

Schaltenberg,

Kumar

et al. 2023

Nat Immunol

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show abstract

“…In mice also lead to decrease of energy expenditure. 34,44 Active infection usually leads to the decrease of energetically expensive movement to make more energy available to the immune system. 45,46 However, caloric restriction has no significant effect on spontaneous physical activity in humans, [47][48][49] and fasting increases locomotor activity of rodents representing a higher exploratory behavior improving the chances to find food in the environment.…”

Section: Discussionmentioning

confidence: 99%

Sustained Inflammation Induced by LPS Leads to Tolerable Anorexia and Fat Loss via Tlr4 in Mice

Yang¹,

Zhong²,

Zhang³

et al. 2022

JIR

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Background Sustained inflammation is implicated in a variety of pathological conditions like infection, obesity and type 2 diabetes. Lipid metabolism is crucial to support immune response during infection of bacteria. However, how sustained inflammation affects lipid metabolism, especially in white adipose tissue remains largely unknown. Methods Sustained inflammation was induced by daily injection of Lipopolysaccharide (LPS). Tlr4 knockout mice were used to study the mechanism. Inflammation and lipid metabolism were evaluated by quantitative PCR, white blood cell counting, nuclear magnetic resonance, fat cell size quantification, lipolysis and fatty acid uptake assays, respiratory exchange ratio, and energy expenditure. Results Here, we found that sustained inflammation leads to fat loss in mice with a quick loss and gradual increase manner. Moreover, LPS injection leads to inflammation, anorexia, decreased lipid anabolism, and increased lipid catabolism. Mechanically, we show that LPS induces fat loss, inflammation, anorexia, and alteration of lipid metabolism mainly dependent on Tlr4 . Interestingly, sustained inflammation induces less fat loss, especially in epididymal white adipose tissue, than pair-feeding, and pair-feeding has no significant effect on inflammation and leads to less fatty acid uptake, more lipid catabolism and energy expenditure than LPS injection. In addition, we demonstrate that short-term sustained inflammation leads to relative long-term tolerance for LPS-induced anorexia, inflammation and altered lipid metabolism. Conclusion These findings demonstrate that sustained inflammation induced by LPS leads to tolerable anorexia and fat loss via Tlr4 in mice, and provide new insights into the effect of sustained inflammation on lipid metabolism and subsequent tolerance.

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“…Fat metabolism is thought to play a role in cell function with specific lipid species either increasing or decreasing the inflammatory state of both myeloid and T cells (Hubler and Kennedy, 2016). In addition, mounting an immune response is thought to be energetically costly and adipose tissue wasting could be a mechanism for lipid mobilization to provide energy for the immune response (Eraud et al, 2005; Ganeshan et al, 2019; Johnson et al, 2021). We found that adipose tissue wasting had no influence on the induction of the immune response in the adipose tissue or spleen in response to a T. brucei infection.…”

Section: Discussionmentioning

confidence: 99%

CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection

Redford

Varanasi

Sanchez

et al. 2022

Preprint

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Catabolic responses of lean and fat energy stores are a component of the host response to infection. Cachexia is an extreme catabolic state characterized by unintentional weight loss and muscle loss, that can include fat loss. Whether cachexia plays any role in host defense or is a maladaptive consequence of host-pathogen interactions remains unknown. Traditionally studies have focused on understanding how inflammatory mediators and cells of the innate immune system contribute to the pathogenesis of cachexia and the depletion of energy stores. The cells of the adaptive immune system that regulate infection-induced cachexia remain elusive. In the present study, we examined the role of the adaptive immune response in cachexia pathogenesis using a murine model of the chronic parasitic infection Trypanosoma brucei, the causative agent of sleeping sickness. We found that the cachectic response occurs in two phases with the first stage occurring early in the infection and involved a loss of body fat mass associated with anorexia, and the second stage occurring later in the infection and involved a sustained loss of fat mass that was accompanied by lean mass wasting. CD4+ T cells were necessary for the development of the sickness-induced anorexic response during stage 1 of the infection, which led to adipose triglyceride lipase dependent lipolysis in adipocytes and the resulting fat wasting. Adipose tissue wasting had no impact on host resistance defenses or survival of infection, both of which were antibody-mediated and independent ofCD4+ T cell responses. Our work reveals a new mechanism for infection induced cachexia involving CD4+ T cell regulation of host feeding behavior and an unexpected decoupling of adaptive immune mediated resistance from the cachectic response during infection.

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The Systemic and Cellular Metabolic Phenotype of Infection and Immune Response to Listeria monocytogenes

Cited by 4 publications

References 72 publications

Short-term dietary changes can result in mucosal and systemic immune depression

Short-term dietary changes can result in mucosal and systemic immune depression

Sustained Inflammation Induced by LPS Leads to Tolerable Anorexia and Fat Loss via Tlr4 in Mice

CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection

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