| Full text | |
| Author(s): Show less - |
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]
Total Authors: 12
|
| Affiliation: | [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
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | Infection and Immunity; v. 77, n. 12, p. 5359-5368, DEC 2009. |
| Web of Science Citations: | 6 |
| Abstract | |
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) | |