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 a-crystallin mAb and mouse rIFN-c, 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-c. Analysis of the lungs showed increased granulomatous infiltration and proinflammatory mediators in anti-IL-4/IgA/IFN-c-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-c-induced activation and nitric oxide production. The described novel immunotherapy, combining treatments with anti-IL-4, IgA antibody and IFN-c, has potential for translation toward the passive immunoprophylaxis of tuberculosis

BUCCHERI S, RELJIC R, CACCAMO N, IVANYI J, SINGH M, SALERNO A, et al. (2007). IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 37(3), 729-737 [10.1002/eji.200636764].

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

BUCCHERI, Simona;CACCAMO, Nadia Rosalia;SALERNO, Alfredo;DIELI, Francesco
2007-01-01

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 a-crystallin mAb and mouse rIFN-c, 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-c. Analysis of the lungs showed increased granulomatous infiltration and proinflammatory mediators in anti-IL-4/IgA/IFN-c-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-c-induced activation and nitric oxide production. The described novel immunotherapy, combining treatments with anti-IL-4, IgA antibody and IFN-c, has potential for translation toward the passive immunoprophylaxis of tuberculosis
2007
BUCCHERI S, RELJIC R, CACCAMO N, IVANYI J, SINGH M, SALERNO A, et al. (2007). IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 37(3), 729-737 [10.1002/eji.200636764].
File in questo prodotto:
File Dimensione Formato  
IL-4 depletion enhances host resistance.pdf

Solo gestori archvio

Dimensione 175.31 kB
Formato Adobe PDF
175.31 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/29805
Citazioni
  • ???jsp.display-item.citation.pmc??? 24
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 50
social impact