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Clinical and Developmental Immunology
Volume 2013, Article ID 781320, 16 pages
Review Article

Immune Vulnerability of Infants to Tuberculosis

1Centre for Understanding and Preventing Infections in Children, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
2Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands
3Sydney Institute for Emerging Infectious Diseases and Biosecurity and The Children's Hospital at Westmead, University of Sydney, Locked Bag 4100, Sydney, NSW 2145, Australia
4Department of Immunology, University of Washington, Seattle, WA 98195, USA
5Seattle Biomedical Research Institute, Seattle, WA 98109, USA
6Department of Pediatrics, University of Washington, Seattle, WA 98195, USA

Received 8 January 2013; Revised 30 March 2013; Accepted 31 March 2013

Academic Editor: Tobias R. Kollmann

Copyright © 2013 Koen Vanden Driessche et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


One of the challenges faced by the infant immune system is learning to distinguish the myriad of foreign but nonthreatening antigens encountered from those expressed by true pathogens. This balance is reflected in the diminished production of proinflammatory cytokines by both innate and adaptive immune cells in the infant. A downside of this bias is that several factors critical for controlling Mycobacterium tuberculosis infection are significantly restricted in infants, including TNF, IL-1, and IL-12. Furthermore, infant T cells are inherently less capable of differentiating into IFN-γ-producing T cells. As a result, infected infants are 5–10 times more likely than adults to develop active tuberculosis (TB) and have higher rates of severe disseminated disease, including miliary TB and meningitis. Infant TB is a fundamentally different disease than TB in immune competent adults. Immunotherapeutics, therefore, should be specifically evaluated in infants before they are routinely employed to treat TB in this age group. Modalities aimed at reducing inflammation, which may be beneficial for adjunctive therapy of some forms of TB in older children and adults, may be of no benefit or even harmful in infants who manifest much less inflammatory disease.