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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Histamine Plays an Essential Regulatory Role in Lung Inflammation and Protective Immunity in the Acute Phase of Mycobacterium tuberculosis Infection

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Carlos, D. [1] ; Fremond, C. [2] ; Samarina, A. [2] ; Vasseur, V. [2] ; Maillet, I. [2] ; Ramos, S. G. [3] ; Erard, F. [2] ; Quesniaux, V. [2] ; Ohtsu, H. [4] ; Silva, C. L. [5] ; Faccioli, L. H. [1] ; Ryffel, B. [2, 6]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil
[2] CNRS, Lab Mol Immunol & Embryol, F-45071 Orleans 2 - France
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Patol, Ribeirao Preto, SP - Brazil
[4] Tohoku Univ, Sendai, Miyagi 980 - Japan
[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto, SP - Brazil
[6] Univ Cape Town, IIDMM, ZA-7925 Cape Town - South Africa
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: Infection and Immunity; v. 77, n. 12, p. 5359-5368, DEC 2009.
Citações Web of Science: 6

The course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Recent data suggest a regulatory role of histamine not only in the innate but also in the adaptive immune response. We used a model of pulmonary Mycobacterium tuberculosis infection in histamine-deficient mice lacking histidine decarboxylase (HDC(-/-)), the histamine-synthesizing enzyme. To confirm that mycobacterial infection induced histamine production, we exposed mice to M. tuberculosis and compared responses in C57BL/6 (wild-type) and HDC(-/-) mice. Histamine levels increased around fivefold above baseline in infected C57BL/6 mice at day 28 of infection, whereas only small amounts were detected in the lungs of infected HDC(-/-) mice. Blocking histamine production decreased both neutrophil influx into lung tissue and the release of proinflammatory mediators, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), in the acute phase of infection. However, the accumulation and activation of CD4(+) T cells were augmented in the lungs of infected HDC(-/-) mice and correlated with a distinct granuloma formation that contained abundant lymphocytic infiltration and reduced numbers of mycobacteria 28 days after infection. Furthermore, the production of IL-12, gamma interferon, and nitric oxide, as well as CD11c(+) cell influx into the lungs of infected HDC(-/-) mice, was increased. These findings indicate that histamine produced after M. tuberculosis infection may play a regulatory role not only by enhancing the pulmonary neutrophilia and production of IL-6 and TNF-alpha but also by impairing the protective Th1 response, which ultimately restricts mycobacterial growth. (AU)

Processo FAPESP: 03/12885-5 - Avaliacao do papel de mastocitos na resposta imune na tuberculose experimental murina.
Beneficiário:Daniela Carlos Sartori
Linha de fomento: Bolsas no Brasil - Doutorado