Interleukin-12 Protects Mice against Disseminated Infection Caused by Paracoccidioides brasiliensis but Enhances Pulmonary Inflammation

Arruda, Celina; Franco, Marcello; Kashino, Suely S.; Nascimento, Flávia R.F.; Fazioli, Raquel dos Anjos; Vaz, Celidéia Aparecida Coppi; Russo, Marco; Calich, Vera Lúcia Garcia

doi:10.1006/clim.2002.5207

Cited by 62 publications

(54 citation statements)

References 41 publications

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“…In addition, Arruda et al [131], demonstrated a dual role for IL-4 in pulmonary paracoccidioidomycosis, as endogenous IL-4 could induce protection or exacerbation of the disease depending on the host genetic pattern. Other study showed that IL-12 protects mice against disseminated infection caused by P. brasiliensis, but enhances pulmonary inflammation [132].…”

Section: Production Of Cytokinesmentioning

confidence: 97%

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

2008

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Section: Production Of Cytokinesmentioning

confidence: 97%

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

2008

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“…IFN-␥ is critical in modulating expression of ICAM-1, 28 -30 being that TNF-␣ 28 -30 and IL-12 11,31,32 are also involved in the up-regulation of expression of this adhesion molecule. Accordingly, mice deficient in the TNF-␣-p55 receptor or in IFN-␥, 7 mice treated with anti-IL-12, 17 and patients deficient in the ␤-1 subunit of the IL-12 receptor 33 all present with increased susceptibility to infection and disseminated disease. These findings suggest that ICAM-1 could be involved in the mechanism of resistance against this fungus.…”

Section: Discussionmentioning

confidence: 99%

“…8 The stimulation of a variety of cells, such as endothelial, mesangial, and bronchial epithelial cells, with inflammatory cytokines [interleukin (IL)-1, TNF-␣, and IFN-␥] increases expression of ICAM-1 12 and favors the transendothelial migration of leukocytes through the interaction with ␤2 integrins. 11,12 The levels of inflammatory cytokines TNF-␣, IL-1, IL-6, IL-12, and IFN-␥ 6,7,[13][14][15][16][17][18][19][20] are increased during the infection with P. brasiliensis. Expression of ICAM-1 is also greatly increased in the lungs of mice infected with conidial forms of P. brasiliensis 21 and is a probably a consequence of the production of proinflammatory cytokines.…”

mentioning

confidence: 99%

Intercellular Adhesion Molecule-1 Is Required for the Early Formation of Granulomas and Participates in the Resistance of Mice to the Infection with the Fungus Paracoccidioides brasiliensis

Moreira

Campanelli

Cavassani

et al. 2006

The American Journal of Pathology

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The migration of leukocytes to inflammatory sites elicited by Paracoccidioides brasiliensis is supposed to be coordinated by cytokines and chemokines. Here, we investigated the role of intercellular adhesion molecule-1 (ICAM-1) in recruiting inflammatory cells to lungs of mice infected with P. brasiliensis and in determining the outcome of the disease. Expression of ICAM-1 was up-regulated on T lymphocytes after infection with the fungus, and its expression was dependent on interferon-␥, tumor necrosis factor-␣, and interleukin-12. Moreover, the absence of ICAM-1 resulted in high susceptibility to the infection and delayed formation of granulomatous lesions. In addition, the absence of ICAM-1 resulted in increased growth and dissemination of fungus , decreased number of CD3 ؉ CD4 ؉ and CD3 ؉ CD8 ؉ T cells , and increased production of interleukin-4 in the inflammatory site. The organization of a granulomatous reaction in mice deficient of ICAM-1 was delayed , starting only on day 60 after infection , whereas in wild-type mice it was complete on day 30 of infection. These data show that ICAM-1 is effectively involved in cellular migration and in the organization of the granulomatous lesion caused by the fungus P.

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“…P. brasiliensis induces an inflammatory response that leads to the formation of granulomas containing a compact collection of cells of the mononuclear phagocytic system, which is the location of the primary lesion in PCM in order to contain and destroy the fungi and prevent its spread. Macrophages and CD4 + T lymphocytes assume central importance in the morphogenesis of the inflammatory process and the synergistic action of these cells is important in the formation and modulation of the granulomas (Ruas et al, 2009;Sadahiro, Diogo, Oshiro, & Shikanai-Yasuda, 2007;Arruda et al, 2002;Romano, Mendes-Giannini, Duarte, & Benard, 2002;Fortes, Kurokawa, Marques, Miot, & Marques, 2011). The CD8 lymphocytes may play an important role in the pathogenesis of pulmonary PCM, because these cells were found in patients with PCM along with pro-inflammatory cytokines produced by alveolar macrophages and specific P. brasiliensis antibodies (Chiarella et al, 2007;Fornazim et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

<b>Influence of n-3 Polyunsaturated Fatty Acid in the Proliferative Activity of Lymphocytes During Experimental Infection with <i>Paracoccidioides brasiliensis

Navarini

Sargi²,

Visentainer

et al. 2018

Acta Sci. Health Sci.

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ABSTRACT. It has been shown that diets containing polyunsaturated omega-3 fatty acids may modulate the immune system. Paracoccidioidomycosis (PCM) is a systemic mycosis of great importance in Latin America, caused by the thermo-dimorphic fungus Paracoccidioides brasiliensis. The aim of this study was to evaluate the influence of n-3 PUFAs in lymphoproliferative activity in murine experimental PCM. Spleen lymphocytes from animals infected with an isolate of P. brasiliensis (Pb18) and fed with diets supplemented with flaxseed oil or a commercial diet for eight weeks, were obtained and cultured for evaluation of lymphoproliferative activity by MTT assay. In uninfected animals and those fed an enriched-flaxseed diet the evaluated lymphoproliferative activity was inhibited in the first week; however, this activity resumed at later stages. On the other hand, in animals infected and fed an enriched-flaxseed diet, the interaction between the stimulus given by the presence of the fungus and the action of n-3 PUFAs appeared to stimulate lymphocyte proliferation after the first week of infection. n-3 PUFAs are shown to influence lymphoproliferative activity of mice in experimental PCM.Keywords: omega-3, paracoccidioidomycosis, imune cell.Influência do ácido graxo poli-insaturado n-3 na atividade proliferativa de linfócitos durante a infecção com Paracoccidioides brasiliensis RESUMO. Tem-se demonstrado que dietas contendo ácido graxo poli-insaturado ômega-3 podem modular o sistema imune. A Paracoccidioidomicose é uma micose sistêmica de grande importância na América Latina, causada pelo fungo termo-dimórfico Paracoccidioides brasiliensis. O objetivo do estudo foi avaliar a influência do AGPI n-3 na atividade linfoproliferativa na PCM experimental murina. Linfócitos esplênicos de animais infectados com o isolado de P. brasiliensis e alimentados com uma dieta suplementada com óleo de linhaça por 8 semanas, foram obtidos e cultivados para avaliação da atividade linfoproliferativa através do ensaio de MTT. Nos animais não infectados e alimentados com a dieta enriquecida com linhaça houve a inibição da atividade linfoproliferativa na primeira semana, sendo retomada no estágio mais tardio. Por outro lado, nos animais infectados e suplementados com a dieta com óleo de linhaça, a interação entre o estímulo dado pela presença do fungo e a ação do AGPI n-3 parecem ter estimulado a proliferação de linfócitos depois da primeira semana de infecção. AGPI n-3 podem ter influenciado a atividade linfoproliferativa dos camundongos na PCM experimental.Palavras-chave: ômega-3, paracoccidioidomicose, células imune.

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Interleukin-12 Protects Mice against Disseminated Infection Caused by Paracoccidioides brasiliensis but Enhances Pulmonary Inflammation

Cited by 62 publications

References 41 publications

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

Intercellular Adhesion Molecule-1 Is Required for the Early Formation of Granulomas and Participates in the Resistance of Mice to the Infection with the Fungus Paracoccidioides brasiliensis

<b>Influence of n-3 Polyunsaturated Fatty Acid in the Proliferative Activity of Lymphocytes During Experimental Infection with <i>Paracoccidioides brasiliensis

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