Current Understanding of Innate Immune Cell Dysfunction in Childhood Undernutrition

Abstract

Undernutrition affects millions of children in low- and middle-income countries (LMIC) and underlies almost half of all deaths among children under 5 years old. The growth deficits that characterize childhood undernutrition (stunting and wasting) result from simultaneous underlying defects in multiple physiological processes, and current treatment regimens do not completely normalize these pathways. Most deaths among undernourished children are due to infections, indicating that their anti-pathogen immune responses are impaired. Defects in the body's first-line-of-defense against pathogens, the innate immune system, is a plausible yet understudied pathway that could contribute to this increased infection risk. In this review, we discuss the evidence for innate immune cell dysfunction from cohort studies of childhood undernutrition in LMIC, highlighting knowledge gaps in almost all innate immune cell types. We supplement these gaps with insights from relevant experimental models and make recommendations for how human and animal studies could be improved. A better understanding of innate immune function could inform future tractable immune-targeted interventions for childhood undernutrition to reduce mortality and improve long-term health, growth and development.

Stunting and Developmental Delays Among Children Aged 6–59 Mo

“…The proportion of stunting in this study was higher than the national prevalence (30.8%) or the Kabupaten Bogor prevalence (28.0%). This finding could indicate that stunted children have a higher risk of mild illness [10], since stunting is found to be related to immunity [11][12][13]. On the other hand, a proportion of suspected developmental delays in this study (44.57%) reconfirmed results from previous studies (6-48%) [14][15][16][17].…”

Impact of Heat-Killed Lactobacillus casei Strain IMAU60214 on the Immune Function of Macrophages in Malnourished Children

“…Protein energy malnutrition (PEM) is also an immunodeficiency that is strongly associated with susceptibility to infections [ 7 , 8 ]. It has been proposed that there is a cause–consequence relationship between immune alterations and malnutrition; however, the effect of cellular alterations on the immune system in malnourished patients has not yet been sufficiently studied [ 9 , 10 ]. In malnourished patients, alterations in the innate immune system have been observed in the epithelial barrier of the skin and intestinal system along with poor granulocyte bactericidal activity, less circulating dendritic cells and reduced complement proteins [ 11 , 12 ].…”

Air pollution and stunting: a missing link?

“…22 Defects in innate and adaptive immune function might then contribute to interrelationships between air pollution, infection, and undernutrition, resulting in a cycle of recurrent illness and malnutrition. 23,24 Specifically, air pollution might impair linear growth through repeated episodes of febrile respiratory illness, which are associated with increased risk of child stunting. 25 It is likely that this association is because of immune activity leading to increased metabolic requirements, anorexia and reduced dietary intake, increased catabolism, and altered metabolism of key nutrients, such as retinol and iron, which are redirected as part of the body's defence mechanisms.…”