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

Simona Buccheri, Rajko Reljic, Nadia Caccamo, Juraj Ivanyi, Mahavir Singh, Alfredo Salerno, Francesco Dieli

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 α-crystallin mAb and mouse rIFN-γ, we observed a 40-fold reduction of the bacterial counts in the lungs at 3 wks following i.n. infection (p-/- 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-γ. Analysis of the lungs showed increased granulomatous infiltration and proinflammatory mediators in anti-IL-4/IgA/ IFN-γ-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-γ-induced activation and nitric oxide production. The described novel immunotherapy, combining treatments with anti-IL-4, IgA antibody and IFN-γ, has potential for translation toward the passive immunoprophylaxis of tuberculosis.

Original languageEnglish
Pages (from-to)729-737
Number of pages9
JournalEuropean Journal of Immunology
Volume37
Issue number3
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Interleukin-4
Immunoglobulin A
Tuberculosis
Infection
Lung
Bacterial Load
Crystallins
Dissent and Disputes
Mycobacterium tuberculosis
Immunotherapy
Nitric Oxide
Spleen
Macrophages
Cytokines
Antibodies
Therapeutics

Keywords

  • Antibodies
  • Bacterial infections
  • Cytokines
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology

Cite this

IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice. / Buccheri, Simona; Reljic, Rajko; Caccamo, Nadia; Ivanyi, Juraj; Singh, Mahavir; Salerno, Alfredo; Dieli, Francesco.

In: European Journal of Immunology, Vol. 37, No. 3, 03.2007, p. 729-737.

Research output: Contribution to journalArticle

Buccheri, S, Reljic, R, Caccamo, N, Ivanyi, J, Singh, M, Salerno, A & Dieli, F 2007, 'IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice', European Journal of Immunology, vol. 37, no. 3, pp. 729-737. https://doi.org/10.1002/eji.200636764
Buccheri, Simona ; Reljic, Rajko ; Caccamo, Nadia ; Ivanyi, Juraj ; Singh, Mahavir ; Salerno, Alfredo ; Dieli, Francesco. / IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice. In: European Journal of Immunology. 2007 ; Vol. 37, No. 3. pp. 729-737.
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