|
| | Role in TB | Relative activity in infants |
|
| Macrophages | Intracellular M.tb killing and growth arrest [38, 210, 211]; alveolar macrophages initiate innate response [212] | Diminished chemotaxis [45] and intracellular killing [56]; reduced numbers of alveolar macrophages [40] |
|
| Neutrophils | Possible role in intracellular M.tb killing
[62, 213–215]; promote T cell priming by facilitating M.tb uptake by DCs [63] | Diminished chemotaxis [65] and intracellular killing [64]; limited neutrophil storage pool [64] |
|
| Dendritic cells | Primary producers of IL-1 and IL-12 [73, 74]; initiate, regulate, and maintain T cell responses [39, 75–77, 216] | Low circulating number [78]; diminished capacity to produce TNF, IL-1, and IL-12 [80, 96, 217]; diminished capacity for priming Th1 cells |
|
| Cell death pathways | Regulate M.tb replication and dissemination [20, 21, 200, 218, 219] | Unknown, but necrotizing granulomas are unusual in infants |
|
| Pattern-recognition receptors | Phagocyte activation [88–90]; trigger cytokine production including TNF, IL-1, IL-12, and IL-10 [95] | Similar expression [98, 99], but altered signaling [100]; reduced triggering of proinflammatory and increased anti-inflammatory cytokines [97, 220] |
|
| TNF | Macrophage activation [20, 21, 103]; promotes immune cell recruitment [105, 106]; regulates cell death pathways [108, 109, 221] | Reduced levels and production capacity [68, 96, 110] |
|
| IL-1 | Intracellular M.tb killing and/or growth arrest [118, 119]; T cell costimulation [125] | Reduced levels and production capacity [96, 222, 223] |
|
| IL-12 | Induction and maintenance of IFN-γ producing T cells [20, 74, 154, 224, 225] | Reduced levels and production capacity [80, 139, 140] |
|
| IL-10 | Restricts Th1 development and impairs IFN-γ-mediated signal transduction [133–135] | Increased levels and production capacity [96, 110, 140] |
|
| Antimicrobial peptides | Direct mycobactericidal activity [142, 143, 226] | Reduced levels and production capacity [152] |
|
| CD4+ T cells | Primary cellular source of IFN-γ and other factors that equip macrophages to restrict intracellular M.tb replication [20, 154, 227, 228]; provide help to maintain CD8+ effector T cells [169] | Bias against Th1 differentiation [172] and for Th2 and Treg induction [176] |
|
| CD8+ T cells | Cytolysis and production of IFN-γ [155, 190, 227] | Diminished IFN-γ production [193] and cytolytic function; bias towards short-lived effectors [192] |
|
| Delayed adaptive immune response | Facilitates prolonged mycobacterial replication and niche establishment in the lung [20, 196] | Infant immune status could even further delay
the response |
|
