Protein Energy Malnutrition Decreases Immunity and Increases Susceptibility to Influenza Infection in Mice

Influenza Division, National Center for Immunization and Respiratory Diseases.
The Journal of Infectious Diseases (Impact Factor: 6). 09/2012; 207(3). DOI: 10.1093/infdis/jis527
Source: PubMed


Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza.

We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model.

We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge.

Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

Full-text preview

Available from:
    • "Fasting reduces B cell progenitors and immature B cells, while mature B cells are less affected[171]. Mice treated with a proteindeficient diet also had a significant reduction in T cell numbers and diminished ability to cope with viral infections[172,173]. Similar observations were made in malnourished children, where CD4 and CD8 T cell counts were significantly reduced in blood[174]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions.
    No preview · Article · Nov 2015 · Seminars in Immunology
  • Source
    • "Within the spleen, total T cell and CD4+ T cell numbers from fasted mice were decreased by 40–50% compared to control animals (85, 86). Additionally, mice fed a protein-deficient diet had atrophic spleens and decreased T cell numbers compared to control mice (87, 88). Decreased T cell numbers observed in fasted mice are mimicked in malnourished human beings. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nutritional status is critically important for immune cell function. While obesity is characterized by inflammation that promotes metabolic syndrome including cardiovascular disease and insulin resistance, malnutrition can result in immune cell defects and increased risk of mortality from infectious diseases. T cells play an important role in the immune adaptation to both obesity and malnutrition. T cells in obesity have been shown to have an early and critical role in inducing inflammation, accompanying the accumulation of inflammatory macrophages in obese adipose tissue, which are known to promote insulin resistance. How T cells are recruited to adipose tissue and activated in obesity is a topic of considerable interest. Conversely, T cell number is decreased in malnourished individuals, and T cells in the setting of malnutrition have decreased effector function and proliferative capacity. The adipokine leptin, which is secreted in proportion to adipocyte mass, may have a key role in mediating adipocyte-T cell interactions in both obesity and malnutrition, and has been shown to promote effector T cell function and metabolism while inhibiting regulatory T cell proliferation. Additionally, key molecular signals are involved in T cell metabolic adaptation during nutrient stress; among them, the metabolic regulator AMP kinase and the mammalian target of rapamycin have critical roles in regulating T cell number, function, and metabolism. In summary, understanding how T cell number and function are altered in obesity and malnutrition will lead to better understanding of and treatment for diseases where nutritional status determines clinical outcome.
    Full-text · Article · Aug 2014 · Frontiers in Immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review examines the best available evidence on the aetiology of childhood acute non-traumatic coma in resource-poor countries (RPCs), discusses the challenges associated with management, and explores strategies to address them. Publications in English and French which reported on studies on the aetiology of childhood non-traumatic coma in RPCs are reviewed. Primarily, the MEDLINE database was searched using the keywords coma, unconsciousness, causality, aetiology, child, malaria cerebral, meningitis, encephalitis, Africa, Asia, and developing countries. 14 records were identified for inclusion in the review. Cerebral malaria (CM) was the commonest cause of childhood coma in most of the studies conducted in Africa. Acute bacterial meningitis (ABM) was the second most common known cause of coma in seven of the African studies. Of the studies in Asia, encephalitides were the commonest cause of coma in two studies in India, and ABM was the commonest cause of coma in Pakistan. Streptococcus pneumoniae was the most commonly isolated organism in ABM. Japanese encephalitis, dengue fever and enteroviruses were the viral agents most commonly isolated. Accurate diagnosis of the aetiology of childhood coma in RPCs is complicated by overlap in clinical presentation, limited diagnostic resources, disease endemicity and co-morbidity. For improved outcomes, studies are needed to further elucidate the aetiology of childhood coma in RPCs, explore simple and practical diagnostic tools, and investigate the most appropriate specific and supportive interventions to manage and prevent infectious encephalopathies.
    No preview · Article · Aug 2013 · Paediatrics and international child health
Show more