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Inflammatory Determinants of Differential Tuberculosis Risk in Pre-Adolescent Children and Young Adults
Richard Baguma1, Stanley Kimbung Mbandi1, Miguel J Rodo1
1South African Tuberculosis Vaccine Initiative (SATVI), Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa.
Insights
Pre-adolescent children have lower myeloid inflammation, making them less susceptible to active tuberculosis (TB) disease compared to young adults. This reduced inflammatory response may explain their lower TB progression risk.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Active tuberculosis (TB) disease progression varies significantly with age, with younger children and adolescents being more susceptible than pre-adolescents.
- The underlying immunological mechanisms driving these age-related differences in TB risk are not fully understood.
Purpose of the Study:
- To investigate age-related differences in pro-inflammatory responses to Mycobacterium tuberculosis (M.tb) infection.
- To determine if lower or more regulated inflammatory responses in pre-adolescent children contribute to their reduced risk of developing active TB disease.
Main Methods:
- Compared inflammatory and antimicrobial mediator levels in pre-adolescent children (8-year-olds) and young adults (18-year-olds) using microfluidic RT-qPCR and protein bead arrays.
- Analyzed published microarray data from TB patients and controls.
- Stimulated whole blood from uninfected children with live M.tb *in vitro*.
Main Results:
- Uninfected 8-year-old children exhibited lower baseline levels of myeloid-associated pro-inflammatory mediators compared to uninfected 18-year-old young adults.
- M.tb infection led to increased myeloid inflammatory responses in children, similar to those observed in adults.
- *In vitro* stimulation confirmed that M.tb induces inflammatory mediator expression in children's blood.
Conclusions:
- Myeloid inflammation is intrinsically lower in pre-pubescent children compared to young adults.
- This reduced or more regulated inflammatory response in children may be a key factor in their lower risk of progressing to active TB disease.
Abstract:
The risk of progression from Mycobacterium tuberculosis (M.tb) infection to active tuberculosis (TB) disease varies markedly with age. TB disease is significantly less likely in pre-adolescent children above 4 years of age than in very young children or post-pubescent adolescents and young adults. We hypothesized that pro-inflammatory responses to M.tb in pre-adolescent children are either less pronounced or more regulated, than in young adults. Inflammatory and antimicrobial mediators, measured by microfluidic RT-qPCR and protein bead arrays, or by analyzing published microarray data from TB patients and controls, were compared in pre-adolescent children and adults. Multivariate analysis revealed that M.tb-uninfected 8-year-old children had lower levels of myeloid-associated pro-inflammatory mediators than uninfected 18-year-old young adults. Relative to uninfected children, those with M.tb-infection had higher levels of similar myeloid inflammatory responses. These inflammatory mediators were also expressed after in vitro stimulation of whole blood from uninfected children with live M.tb. Our findings suggest that myeloid inflammation is intrinsically lower in pre-pubescent children than in young adults. The lower or more regulated pro-inflammatory responses may play a role in the lower risk of TB disease in this age group.
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