Role of interleukin-10 in the modulation of the airway immune response during lung bacterial infection

Bacterial pneumonia is a major death cause worldwide. It has been classified in community-acquired pneumonia (CAPs) and hospital-associated pneumonia (HAPs). Klebsiella pneumoniae-ST258 (CRKP-ST258) is a main cause of HAPs. Using a clinical isolate of CRKP-ST258 (KP35) we demonstrated the ability of KP35 to evade the killing mediated by neutrophils. Besides, we identified that the early recruited Monocytic-Myeloid-derived suppressor cells (M-MDSCs) suppress neutrophil function in vitro and are essential to modulate the immune response in mice and promotes host survival through the production of Interleukin-10.

On the other side, Streptococcus pneumoniae is the major cause of CAP. Some data suggest that the strong inflammatory immune response observed during pneumococcal pneumonia facilitates bacterial dissemination. According to this idea, we evaluated the role of the anti-inflammatory cytokine Interleukin-10 during pneumococcal pneumonia. Our data demonstrate that the production of IL-10 improves host survival, modulates the recruitment of neutrophils to the lung tissue and reduces lung injury. Interestingly, IL-10 production impairs bacterial clearance and promotes bacterial dissemination. We next characterized the infiltrating population of neutrophils to the lungs during S. pneumoniae, describing two neutrophil subsets, named N1 and N2; which have different size, granularity and activation.

Moreover, N2, but not N1 neutrophils produce IL-10 in response to . pneumoniae. In summary, this thesis provides strong evidence about the ability of CRKP-ST258 to evade neutrophils and monocytes; and the importance of IL-10 production in host survival during pneumonia caused by either K. pneumoniae or S. pneumoniae.

• Nombre: Hernán Peñaloza Cerda
• Laboratorio: Patogénesis Microbiana
• Mención: Genética Molecular y Microbiología
• Director Tesis: Susan Bueno