| First Author | Buccheri S | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 3 | Pages | 729-37 |
| PubMed ID | 17304630 | Mgi Jnum | J:118651 |
| Mgi Id | MGI:3700071 | Doi | 10.1002/eji.200636764 |
| Citation | Buccheri S, et al. (2007) IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice. Eur J Immunol 37(3):729-37 |
| abstractText | The influence of Th2 cytokines in tuberculosis has been a matter of dispute. Here we report that IL-4 has a profound regulatory effect on the infection of BALB/c mice with Mycobacterium tuberculosis. Depletion of IL-4 with a neutralizing mAb caused only evanescent reduction of lung infection, but when combined with i.n. inoculations of IgA anti-mycobacterial alpha-crystallin mAb and mouse rIFN-gamma, we observed a 40-fold reduction of the bacterial counts in the lungs at 3 wks following i.n. infection (p<0.001). In genetically deficient IL-4(-/-) BALB/c mice, infection in both lung and spleen was substantially reduced for up to 8 wks without further treatment. Reconstitution of IL-4(-/-) mice with rIL-4 increased bacterial counts to wild-type levels and made the mice refractory to protection by IgA/IFN-gamma. Analysis of the lungs showed increased granulomatous infiltration and proinflammatory mediators in anti-IL-4/IgA/IFN-gamma-treated and infected mice. We conclude that the action of IL-4 in tuberculosis is targeted at macrophages and that it may include an antagonistic effect on their IgA/IFN-gamma-induced activation and nitric oxide production. The described novel immunotherapy, combining treatments with anti-IL-4, IgA antibody and IFN-gamma, has potential for translation toward the passive immunoprophylaxis of tuberculosis. |
