Search

Mice of I/St strain develop severe lung inflammation and die shortly following infection with virulent mycobacteria. To find out whether tuberculosis (TB)-susceptible I/St mice are susceptible to other intracellular bacteria, we investigated two different taxonomically distant pathogens, Chlamydia pneumoniae and Salmonella enterica serovar Typhimurium. Comparison of I/St and TB-resistant A/Sn mice (both Nramp1r) demonstrated that the former are more susceptible to both salmonella and chlamydia, displaying a significantly shortened survival time following challenge. Lung pathology develops more rapidly in I/St compared to A/Sn mice following infection with chlamydia, despite their similar ability to control bacterial multiplication. Following infection with salmonella, substantial (∼ 3 log) but very short (second day post-infection) interstrain differences in bacterial loads were observed, accompanied by higher levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in the peritoneal cavities of I/St mice. I/St macrophages were more permissive for salmonella growth during the first 24 h following infection in vitro. Because the prominent differences in survival time did not correlate with permanent differences in bacterial multiplication, we suggest that both infections trigger fatal pathological processes whose dynamics depend strongly upon the host genetics. [ABSTRACT FROM AUTHOR]

Protection against tuberculosis depends upon the generation of CD4+ T cell effectors capable of producing IFN-γ and stimulating macrophage antimycobacterial function. Effector CD4+ T cells are known to express CD44hiCD62Llo surface phenotype. In this paper we demonstrate that a population of CD44hiCD62Llo CD4+ effectors generated in response toMycobacterium bovisBCG orM. tuberculosisinfection in C57BL/6 mice is heterogeneous and consists of CD27hi and CD27lo T cell subsets. These subsets exhibit a similar degree ofin vivoproliferation, but differ by the capacity for IFN-γ production.Ex vivoisolated CD27lo T cells express higher amounts of IFN-γ RNA and contain higher frequencies of IFN-γ producers compared to CD27hi subset, as shown by real-time PCR, intracellular staining for IFN-γ and ELISPOT assays. In addition, CD27lo CD4+ T cells uniformly express CD44hiCD62Llo phenotype. We propose that CD27lo CD44hiCD62Llo CD4+ T cells represent highly differentiated effector cells with a high capacity for IFN-γ secretion and antimycobacterial protection at the site of infection. [ABSTRACT FROM AUTHOR]