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.
Institutional repository IRUAKVD is supported by an ESPID Fellowship Award. BSQ is supported by a University of British Columbia-Cystic Fibrosis Canada Clinician-Scientist Award and receives grant monies from the British Columbia Lung Association. MFC received grants from Gilead, ViiV, BMS, Novartis, and VPM, all outside the study we report here. JEAZ receives salary support from Cystic Fibrosis Canada. The authors declare no conflicts of interest.
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