Table 2.
Role of IL-36 cytokines during lung bacterial and viral infection and their effect in lung immunity and host survival.
| Pathogen | IL-36 cytokine involved | Cellular source(s) | Effect in host survival | Effect in pathogen clearance | Effect in lung inflammation | Effect in cytokine production | Effect in immune cell recruitment/activation | References |
|---|---|---|---|---|---|---|---|---|
| Bacterial | ||||||||
| Strepcococcus pneumoniae | IL-36γ | Lung resident macrophage | Promotes survival | Improves bacterial clearance | Unknown | Induces | Activation of macrophages. No effect in cell recruitment. | (22, 75) |
| IL-12p40 IL-23p19 IL-17 TNF-α | ||||||||
| IP-10 | ||||||||
| IFN-γ | ||||||||
| Klebsiella pneumoniae | IL-36γ | Lung resident macrophage | Promotes survival | Improves bacterial clearance | Unknown | Induces | Unknown | (22, 75) |
| IL-12 | ||||||||
| IL-23 | ||||||||
| IFN-γ | ||||||||
| Legionella pneumophila | IL-36α | Unknown | Promote survival | Improve bacterial clearance | Reduce lung injury | Unknown | Enhance neutrophil, monocyte and macrophages recruitment. Enhanced macrophage polarization and activation. | (71) |
| IL-36γ | ||||||||
| Mycobacterium bovis BCG | Unknown | Unknown | None | None | Reduce lung injury | Induce | Unknown | (65, 76) |
| IL-6 | ||||||||
| TNF-α | ||||||||
| IFN-γ | ||||||||
| Mycobacterium tuberculosis | IL-36γ | Macrophage | None | Improves bacterial clearance by macrophages in vitro | None | None | Enhances production of antimicrobial peptides by macrophages through LXR pathway. | (68, 69, 76) |
| Lung epithelial cells | ||||||||
| Pseudomonas aeruginosa | IL-36γ | Lung resident macrophage | Reduces survival | Impairment of bacterial clearance | Increase lung injury | Induces TNF-α IL-6 |
Impairs antimicrobial ability on macrophages through COX-2 activation and PGE2 production. | (77) |
| Alveolar epithelial cells | IL-17 IL-10 |
|||||||
| Viral | ||||||||
| Influenza virus | IL-36α IL-36β IL-36γ |
Alveolar epithelial cells | Opposite results | Impairment of viral clearance | 1.IL-36R-/- mice showed reduced lung injury compared to WT mice | Induce IL-17 |
Enhanced neutrophil infiltration Impaired T cell activation | (70, 78) |
| Neutrophils | 1. L-36R-/- mice improved survival. IL-36γ-/- mice show equivalent survival compared to WT mice | 2. IL-36γ-/- mice showed severe lung injury compared to WT mice | Increased macrophage apoptosis | |||||
| 2. IL-36γ-/- mice showed improved survival compared to WT mice. | CXCL-1 | M1 macrophage polarization. | ||||||
| IP-10 Reduced | ||||||||
| IFN-β Opposite results found in IL-6 |