title: Immune vulnerability of infants to tuberculosis.
abstract: 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.
authors.affiliation: Centre for Understanding and Preventing Infections in Children, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4. koen.vandendriessche@cw.bc.ca
authors.forename: Koen
authors.initials: K
authors.lastname: Vanden Driessche
authors.forename: Alexander
authors.initials: A
authors.lastname: Persson
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Marais
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Fink
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Urdahl
mesh_terms: D000328:Adult; D000367:Age Factors; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004198:Disease Susceptibility; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D000995:Antitubercular Agents; D007155:Immunologic Factors; D007375:Interleukin-1; D018664:Interleukin-12; D007371:Interferon-gamma