Production of pro-inflammatory cytokines during the early stages of experimentalParacoccidioides brasiliensisinfection

Abstract

Pro-inflammatory cytokines play an important role in both recruitment and activation of leukocytes migrating into tissues in response to invading pathogens. In this study the production of pro-inflammatory cytokines, determined by ELISA assays, and the recruitment of leukocytes into the lungs of BALB/c mice infected with Paracoccidioides brasiliensis conidia were evaluated during the early stages of infection. The results showed that infected mice had a significant increase in leukocytes in the lung during the first 4 days with a peak at day 2 post-challenge; infiltrates were composed mainly of polymorphonuclear neutrophils (PMN). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF-alpha), interleukin (IL) 6, IL-1beta and macrophage inflammatory protein (MIP) 2 were produced at elevated levels during the first 4 days post-challenge, but only in pulmonary samples and not in sera. Additionally, during the early stages of infection, overall weight loss was recorded in infected mice. These results suggest that pro-inflammatory cytokines could be responsible for the recruitment of leukocytes into the lung during the early stages of P. brasiliensis infection. In addition, both pro-inflammatory cytokine production and leukocyte recruitment may participate in the control of infection by influencing the organization of the immune response in the host exposed to P. brasiliensis conidia.

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

“…We have also observed that after intranasal challenge with P. brasiliensis conidia, the cellularity of bronchoalveolar lavage fluid (BAL) increased [29]. The majority of these pro-inflammatory leukocytes in BAL fluids of infected mice were PMNs.…”

“…Even if the early inflammatory response is nonspecific, such a stage is important because it is just at this moment that the resident pulmonary macrophages interact with the fungus for the first time and become activated proceeding to stimulate recruitment of other inflammatory cells [27][28][29][30]. In summary, the observations described above establish the value of this animal model for studies of the immune responses in PCM, and may contribute to designing new, more far reaching experiments.…”

Paracoccidioidomicose em hemisfério cerebral e tronco encefálico: relato de caso

“…As citocinas pró-inflamatórias, como fator de nec rose tumoral alfa (TNF-alfa), IL-6, IL-1 beta e pro t e í n a inflamatória do macrófago (MIP) 2, seriam re s p o n s á-veis pelo re c rutamento de leucócitos em nível pulmon a r, durante a fase inicial da infecção e influenciariam na organização da resposta imune, na presença do fungo 10 .…”

Paracoccidioides lutzii: estudo de alguns mecanismos de patogenicidade

“…A coleção dos conídios para experimentação normalmente é feita por dois métodos: o método de lã de vidro e a purificação por gradientes de percoll (18,100,101). Nós trabalhamos somente com purificação por lã de vidro, que é a metodologia mais apropriada para o trabalho com modelo animal.…”

“…Para a infecção com propágulos foi adotado o modelo da infecção intranasal descrito previamente (20,100,105). Os animais foram anestesiados e, quando se apresentaram insensíveis à dor, os conídios, cuja concentração foi ajustada para 4x10 6 células/60µl, foi administrada intranasalmente (i.n.)…”