IL-4 subverts mycobacterial containment in Mycobacterium tuberculosis-infected human macrophages.

Protective immunity against Mycobacterium tuberculosis is poorly understood. The role of interleukin (IL)-4, the archetypal T-helper type 2 (Th2) cytokine, in the immunopathogenesis of human tuberculosis remains unclear.Blood and/or bronchoalveolar lavage fluid (BAL) were obtained from participants with pulmonary tuberculosis (TB) (n=23) and presumed latent TB infection (LTBI) (n=22). Messenger RNA expression levels of interferon (IFN)-γ, IL-4 and its splice variant IL-4δ2 were determined by real-time PCR. The effect of human recombinant (hr)IL-4 on mycobacterial survival/containment (CFU·mL-1) was evaluated in M. tuberculosis-infected macrophages co-cultured with mycobacterial antigen-primed effector T-cells. Regulatory T-cell (Treg) and Th1 cytokine levels were evaluated using flow cytometry.In blood, but not BAL, IL-4 mRNA levels (p=0.02) and the IL-4/IFN-γ ratio (p=0.01) was higher in TB versus LTBI. hrIL-4 reduced mycobacterial containment in infected macrophages (p<0.008) in a dose-dependent manner and was associated with an increase in Tregs (p<0.001), but decreased CD4+Th1 cytokine levels (CD4+IFN-γ+ p<0.001; CD4+TNFα+ p=0.01). Blocking IL-4 significantly neutralised mycobacterial containment (p=0.03), CD4+IFNγ+ levels (p=0.03) and Treg expression (p=0.03).IL-4 can subvert mycobacterial containment in human macrophages, probably via perturbations in Treg and Th1-linked pathways. These data may have implications for the design of effective TB vaccines and host-directed therapies

The OP27 cell line as a model system to study the effects of FGF-2 in olfactory neuronal development

Includes bibliographical references.Due to its unique capacity to regenerate continously, the olfactory neuroepithelium serves as an excellent model system for investigating the molecular and cellular mechanisms involved in neurogenesis. The OP27 cell line (generated by infecting embryonic mouse olfactory placodes with a retrovirus carrying the temperature-sensitive alleles of the SV 40 large T antigen) was used as an in vitro system to test the effects of fibroblast growth factor-2 (FGF-2) in directing olfactory neurogenesis. The OP27 cells proliferate under the control of the retrovirus at the permissive temperature (33°C). When shifted to the non-permissive temperature (39°C) the SV40 large T antigen is inactivated and the cells stop dividing, thereby allowing one to study the effects of growth factors on these cells. Although FGF-2 also plays an important role in regulating the proliferation of neural progenitors, the main focus in this study was its effect on neuronal differentiation