Abstract

Cellular immunity is critical for protection against tuberculosis, but its integrity is compromised during undernutrition. The present study was designed to evaluate if the attenuated mycobacterium BCG is a safe vaccine for undernourished individuals. An experimental model of undernutrition was established by subjecting BALB/c mice to dietary restriction. These animals received 70% of the amount of food consumed by the healthy control group and exhibited physiological alterations compatible with malnutrition, including body weight loss, reduced levels of triglycerides and glucose, and reduced lymphocyte numbers. Undernourished mice were immunized with BCG, and the mycobacterial loads in lymph nodes, spleen, liver, lungs, and thymus were determined. A much higher proportion of undernourished mice exhibited bacterial dissemination to the lymph nodes, spleen and liver. In addition, only undernourished animals had bacteria in the lungs and thymus. Concomitant with higher mycobacterial loads and more widespread BCG dissemination in undernourished mice, production of TNF-α, IFN-γ, and IL-10 was also diminished in these mice. Taken together, these results indicate that BCG infection is more severe in undernourished mice. Whether a similar phenomenon exists in undernourished children or not remains to be thoroughly investigated.

Highlights

  • Undernutrition is one of the major causes of mortality and morbidity worldwide

  • Protein-energy malnutrition (PEM) impairs, for example, cytokine production, T-cell function, and the ability of lymphocytes to appropriately respond to these cytokines [5]

  • We previously reported that both DNAhsp65 and Bacillus CalmetteGuerin (BCG) could prime newborn mice for stronger immune responses to DNAhsp65 boosters at the adult stage [13]

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Summary

Introduction

Undernutrition is one of the major causes of mortality and morbidity worldwide. Protein-energy malnutrition (PEM) is the most common type of undernutrition and is caused by deficiencies in protein or macro- and micronutrients such as vitamin A, vitamin E, vitamin B6, folate, zinc, iron, copper, and selenium [2]. Inadequate energy intake leads to various physiological deficiencies, such as growth deficiencies and loss of fat, muscle and visceral mass, and has deleterious effects on the immune system [3]. Undernutrition has been linked to many deficiencies of the innate immunity as decreased lysozyme production by monocytes and polymorphonuclear cells (PMNs), depletion of complement components, and impairment of macrophage functions [4]. PEM impairs, for example, cytokine production, T-cell function, and the ability of lymphocytes to appropriately respond to these cytokines [5]

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