Dual role of interleukin-4 (IL-4) in pulmonary paracoccidioidomycosis: Endogenous IL-4 can induce protection or exacerbation of disease depending on the host genetic pattern

Dual role of interleukin-4 (IL-4) in pulmonary paracoccidioidomycosis: Endogenous IL-4 can induce protection or exacerbation of disease depending on the host genetic pattern

Autor Arruda, Celina Google Scholar
Valente-Ferreira, Rita. C. Google Scholar
Pina, Adriana Google Scholar
Kashino, Suely S. Google Scholar
Fazioli, Raquel A. Google Scholar
Vaz, Celideia AC Google Scholar
Franco, Marcello F. Autor UNIFESP Google Scholar
Keller, Alexandre C. Google Scholar
Calich, Vera LG Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo Resistance to paracoccidioidomycosis, the most important endemic mycosis in Latin America, is thought to be primarily mediated by cellular immunity and the production of gamma interferon. To assess the role of interleukin-4 (IL-4), a Th2 cytokine, pulmonary paracoccidioidomycosis in IL-4-depleted susceptible (B10.A) and intermediate (C57BL/6) mice was studied. Two different protocols were used to neutralize endogenous IL-4 in B10.A mice: I mg of anti-IL-4 monoclonal antibody (MAb)/week and 8 mg I day before intratracheal infection with 106 Paracoccidioides brasiliensis yeast cells. Unexpectedly, both protocols enhanced pulmonary infection but did not alter the levels of pulmonary cytokines and specific antibodies. Since in a previous work it was verified that C57BL/6 mice genetically deficient in IL-4 were more resistant to P. brasiliensis infection, we also investigated the effect of IL-4 depletion in this mouse strain. Treatment with the MAb at 1 mg/week led to less severe pulmonary disease associated with impaired synthesis of Th2 cytokines in the lungs and liver of control C57BL/6 mice. Conversely, in IL-4-depleted C57BL/6 mice, increased levels of tumor necrosis factor alpha and IL-12 were found in the lungs and liver, respectively. in addition, higher levels of immunoglobulin G2a (IgG2a) and lower levels of IgG1 antibodies were produced by IL-4-depleted mice than by control mice. Lung pathologic findings were equivalent in IL-4-depleted and untreated B10.A mice. in IL-4-depleted C57BL/6 mice, however, smaller and well-organized granulomas replaced the more extensive lesions that developed in untreated mice. These results clearly showed that IL-4 can have a protective or a disease-promoting effect in pulmonary paracoccidioidomycosis depending on the genetic background of the host.
Idioma Inglês
Data de publicação 2004-07-01
Publicado em Infection and Immunity. Washington: Amer Soc Microbiology, v. 72, n. 7, p. 3932-3940, 2004.
ISSN 0019-9567 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Microbiology
Extensão 3932-3940
Fonte http://dx.doi.org/10.1128/IAI.72.7.3932-3940.2004
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000222282800029
Endereço permanente http://repositorio.unifesp.br/handle/11600/27806

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