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Front. Immunol. | doi: 10.3389/fimmu.2018.02946

The Wonder Years: What Can Primary School Children Teach Us about Immunity to Mycobacterium tuberculosis?

  • 1Imperial College London, United Kingdom
  • 2Brown University, United States
  • 3University of Oxford, United Kingdom
  • 4The University of Melbourne, Australia

In high burden settings, the risk of infection with Mycobacterium tuberculosis increases throughout childhood due to cumulative exposure. However, the risk of progressing from tuberculosis (TB) infection to disease varies by age. Young children (<5 years) have high risk of disease progression following infection. The risk falls in primary school children (5 to <10 years), but rises again during puberty. TB disease phenotype also varies by age: generally, young children have intrathoracic lymph node disease or disseminated disease, while adolescents (10 to <20 years) have adult-type pulmonary disease. TB risk also exhibits a gender difference: compared to adolescent boys, adolescent girls have an earlier rise in disease progression risk and higher TB incidence until early adulthood. Understanding why primary school children, during what we term the ‘Wonder Years,’ have low TB risk has implications for vaccine development, therapeutic interventions, and diagnostics. To understand why this group is at low risk, we need a better comprehension of why younger children and adolescents have higher risks, and why risk varies by gender. Immunological response to M. tuberculosis is central to these issues. Host response at key stages in the immunopathological interaction with M. tuberculosis influences risk and disease phenotype. Cell numbers and function change dramatically with age and sexual maturation. Young children have poorly functioning innate cells and a Th2 skew. During the “Wonder Years”, there is a lymphocyte predominance and a Th1 skew. During puberty, neutrophils become more central to host response, and CD4+ T cells increase in number. Sex hormones (dehydroepiandrosterone, adiponectin, leptin, oestradiol, progesterone, and testosterone) profoundly affect immunity. Compared to girls, boys have a stronger Th1 profile and increased numbers of CD8+ T cells and NK cells. Girls are more Th2-skewed and elicit more enhanced inflammatory responses. Non-immunological factors (including exposure intensity, behaviour, and co-infections) may impact disease. However, given the consistent patterns seen across time and geography, these factors likely are less central. Strategies to protect children and adolescents from TB may need to differ by age and sex. Further work is required to better understand the contribution of age and sex to M. tuberculosis immunity.

Keywords: Tuberculosis, Children, Infection, Immunity, protection, Mycobacerium tuberculosis, Vaccination, adolescence

Received: 18 Jul 2018; Accepted: 30 Nov 2018.

Edited by:

Thomas R. Hawn, University of Washington, United States

Reviewed by:

Shashank Gupta, Brown University, United States
David Horne, University of Washington, United States  

Copyright: © 2018 Seddon, Chiang, Esmail and Coussens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. James A. Seddon, Imperial College London, London, United Kingdom, james.seddon@imperial.ac.uk