IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice.

Abstract:

: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.

journal_name

Eur J Immunol

authors

Buccheri S,Reljic R,Caccamo N,Ivanyi J,Singh M,Salerno A,Dieli F

doi

10.1002/eji.200636764

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

729-37

issue

3

eissn

0014-2980

issn

1521-4141

journal_volume

37

pub_type

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