Table 4.
Th17-related effects in preclinical tuberculosis (TB) studies in mice.
| Mice (age, weeks) | Intervention | Mtb strain, route | Survival | Mtb load (vs. wild-type mice) | Immunological effect | Reference |
|---|---|---|---|---|---|---|
| B6 (6–12) | IL23 p19−/− |
H37Rv (100 CFU), aerosol | No data | No difference in lungs | No IL-17-producing cells in lungs up to day 150 | Khader et al. (158) |
| 1 log higher Mtb load in spleen at day 150 | ||||||
| B6 (6–12) | IL23 p19−/− |
H37Rv (100 CFU), aerosol | No data | Day 120 and onward, 0.5–1 log higher Mtb load in lungs | Reduced no. of B-cell follicles at day 200 (Cxcl13 mediated) | Khader et al. (194) |
| Strongly impaired IL-17, IL-22 production in lungs up to day 250 | ||||||
| B6 (6–12) | IL22−/− | H37Rv (100 CFU), aerosol | No data | No effect up to day 200 | Suboptimal B-cell follicle development (Cxcl13-mediated) | Khader et al. (194) |
| B6 (6–9) | IL-17 RA−/− |
H37Rv (1.103 CFU), i.t. | Higher mortality (median survival: 18 vs. 35 weeks) | 1.5 log higher Mtb load at week 12 and week 20 in lungs | Impaired cell recruitment (PMN, lymphocytes, Mo/DC) | Freches et al. (195) |
| Increased IL-1β | ||||||
| Decreased TNF-α, IL-6 and IL-10 | ||||||
| B6 (6–12) | IL-17 RA−/− |
H37Rv (100 CFU), aerosol | No data | No effect up to day 200 | Suboptimal B-cell follicle development (Cxcl13-mediated) | Khader et al. (194) |
| B6 (8–12) | IL-17−/− | H37Rv (1.103 CFU), i.t. | No data | 1.5 log higher Mtb load | Reduced no. of granulomas at day 28 | Okamoto Yoshida et al. (196) |
| B6 (6–8) | IL-17−/− | HN878 (100 CFU), aerosol | No data | 1 log higher Mtb load in lungs at day 30 0.5 log higher Mtb load in lungs at day 60 |
Infection with HN878 showed robust production of IL-1β through TLR2, which supported increased IL-17 production compared to H37Rv and CDC1551 | Gopal et al. (197) |
| B6 (6–8) | IL-17−/− | H37Rv, CDC1551 (100 CFU), aerosol | No data | No difference at day 30 and day 60 | Gopal et al. (197) | |
| B6 (8–12) | IL-17−/− | H37Rv (1.103 CFU), i.t. | Higher mortality | 1.5 log higher Mtb loads in lungs at day 30, 1 log higher Mtb loads at day 60 and day 120 | Impaired granuloma formation, γδ T-cells primary source of IL-17 | Umemura et al. (198) |
Red text indicates a harmful effect to the host; CFU, colony forming units; IL-17RA, IL-17 receptor A; i.t., intratracheal instillation.