Evaluation of the ability of neutrophils to induce an anti-inflammatory response in the airways through the recognition of molecular patterns of Streptococcus pneumoniae
Streptococcus pneumoniae is the bacterial agent mostly associated with community-acquired pneumonia in the world. This microorganism has several virulence factors, differentially expressed to colonize the respiratory tract and evade the immune response, contributing to the development of lung diseas...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | Chile |
| OAI Identifier: | oai:repositorio.anid.cl:10533/246490 |
| Acceso en línea: | https://hdl.handle.net/10533/246490 |
| Access Level: | acceso abierto |
| Palabra clave: | Ciencias Naturales Otras Ciencias Naturales |
| Sumario: | Streptococcus pneumoniae is the bacterial agent mostly associated with community-acquired pneumonia in the world. This microorganism has several virulence factors, differentially expressed to colonize the respiratory tract and evade the immune response, contributing to the development of lung disease. Pneumococcal pneumonia is characterized by the induction of a high influx of neutrophils into the alveoli, and this phenomenon is associated with inflammation and lung tissue damage. Neutrophils, widely recognized for their pro-inflammatory properties, have been highlighted in recent studies for being versatile cells able to modulate the immune response, for example, through the production of IL-10. IL-10 is an anti-inflammatory cytokine, which has been shown to have a dual role during pneumococcal pneumonia, reiterating the need to know the factors involved in its regulation. To determine the factors involved in the regulation of IL-10 production, during this thesis, the cells that are involved in IL-10 production during the infectious process were evaluated and it was determined that neutrophils contribute significantly to the increase of the levels of expression of IL-10 observed in the 24 h after infection with S. pneumoniae. A characterization of neutrophils was performed, which evidenced that these cells constitute an heterogeneous population, in which at least two subtypes are distinguished that differ both morphologically and in their ability to produce IL-10. Besides, adoptive neutrophil transfer assays were performed in mice unable to produce IL-10, to determine the role of neutrophils producing this cytokine during pneumococcal pneumonia. The results obtained in these experiments demonstrated that neutrophil transfer from wild-type (capable of producing IL-10) to IL-10-/- mice (highly susceptible to infection) promoted lung recovery and protected IL-10-/- mice from pneumonia. On the other hand, it was observed that IL-10-/- mice transferred with WT cells showed a reduced bacterial clearance when compared with the other IL-10-/- groups. These results indicate that neutrophils capable of producing IL-10 could be modulating the immune response and playing a critical role during the first 48 h after S. pneumoniae lung infection. Finally, to determine the factors involved in the induction of IL-10, in vitro tests were performed to assess whether the stimulus comes from the host, the bacteria, or if both were necessary. The results of these experiments showed that in vitro, only molecules from S. pneumoniae induce the production of IL-10 in neutrophils. Taken together, the results of this thesis suggest that S. pneumoniae, through the recognition of its molecules, induce the production of IL-10 in neutrophils and this fact plays a crucial role in the outcome of pneumonia. |
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