Effect of Transforming Growth Factor β on Experimental Salmonella typhimurium Infection in Mice

We have investigated the effect of the in vivo administration of recombinant transforming growth factor β (rTGF-β) on the pathogenic mechanisms involved in Salmonella typhimurium experimental infection in mice. The protective response elicited by macrophages was induced by rTGF-β(1) by 2 days after experimental infection, as demonstrated by an increased NO production, while the humoral protective effect began with cytokine mRNA expression 2 days after the challenge and continued after 5 days with cytokine release and lymphocyte activation. We demonstrated that all mice who received rTGF-β(1) survived 7 days after infection. The number of bacteria recovered in the spleens and in the livers of rTGF-β(1)-treated mice 2 and 5 days after infection was significantly smaller than that found in the same organs after phosphate-buffered saline (PBS) inoculation. Furthermore, 2 and 5 days after infection, splenic macrophages from rTGF-β(1)-treated mice showed a greater NO production than did those from PBS-treated mice. The effect of rTGF-β(1) on S. typhimurium infection in mice was correlated with the expression of cell costimulatory CD28 molecules. Five days after S. typhimurium infection, the percentage of CD28(+)-expressing T cells in splenic lymphocytes from rTGF-β(1)-treated mice increased with respect to that from control mice. Gamma interferon (IFN-γ) mRNA was present in a greater amount in spleen cells from rTGF-β(1)-treated mice after 2 days, although the intensity of the band decreased 5 days after the challenge. A similar pattern was obtained with the mRNAs for interleukin-1α (IL-1α), IL-6, TGF-β, and inducible nitric oxide synthase, which showed greater expression in cells obtained from rTGF-β(1)-treated and S. typhimurium-infected mice 2 days after challenge. The treatment with rTGF-β(1) induced an increase in IL-1α and IFN-γ release in the supernatant of splenocyte cultures 5 days after the experimental infection with S. typhimurium. Moreover, we demonstrated that 5 days after infection, the IFN-γ titer was significantly greater in the sera of rTGF-β-treated mice than in those of PBS-treated mice. Also, hsp60 showed greater expression 2 days after the challenge in splenocytes from rTGF-β(1)-treated mice. The role played by proinflammatory and immunoregulatory cytokines and by CD28 is discussed.