| First Author | Perez-Toledo M | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 3 | Pages | 708-719 |
| PubMed ID | 32591391 | Mgi Jnum | J:300397 |
| Mgi Id | MGI:6502342 | Doi | 10.4049/jimmunol.2000089 |
| Citation | Perez-Toledo M, et al. (2020) Mice Deficient in T-bet Form Inducible NO Synthase-Positive Granulomas That Fail to Constrain Salmonella. J Immunol 205(3):708-719 |
| abstractText | Clearance of intracellular infections caused by Salmonella Typhimurium (STm) requires IFN-gamma and the Th1-associated transcription factor T-bet. Nevertheless, whereas IFN-gamma(-/-) mice succumb rapidly to STm infections, T-bet(-/-) mice do not. In this study, we assess the anatomy of immune responses and the relationship with bacterial localization in the spleens and livers of STm-infected IFN-gamma(-/-) and T-bet(-/-) mice. In IFN-gamma(-/-) mice, there is deficient granuloma formation and inducible NO synthase (iNOS) induction, increased dissemination of bacteria throughout the organs, and rapid death. The provision of a source of IFN-gamma reverses this, coincident with subsequent granuloma formation and substantially extends survival when compared with mice deficient in all sources of IFN-gamma. T-bet(-/-) mice induce significant levels of IFN-gamma(-) after challenge. Moreover, T-bet(-/-) mice have augmented IL-17 and neutrophil numbers, and neutralizing IL-17 reduces the neutrophilia but does not affect numbers of bacteria detected. Surprisingly, T-bet(-/-) mice exhibit surprisingly wild-type-like immune cell organization postinfection, including extensive iNOS(+) granuloma formation. In wild-type mice, most bacteria are within iNOS(+) granulomas, but in T-bet(-/-) mice, most bacteria are outside these sites. Therefore, Th1 cells act to restrict bacteria within IFN-gamma-dependent iNOS(+) granulomas and prevent dissemination. |
