Abstract
Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10-/-) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.
Highlights
Pneumonia is defined as an inflammatory condition affecting the lower respiratory tract and is considered the leading cause of death due to infections in children under five years of age [1, 2]
Based on the potential immunomodulatory role of neutrophils mediated by the production of IL-10, in the present study we evaluated whether the production of IL-10 by neutrophils recruited to the lungs in response to S. pneumoniae infection downmodulates inflammation of this tissue and promotes host survival
In agreement with the literature, here we report the existence of heterogeneous population of neutrophils that produce IL-10 in the lungs during S. pneumoniae infection
Summary
Pneumonia is defined as an inflammatory condition affecting the lower respiratory tract and is considered the leading cause of death due to infections in children under five years of age [1, 2]. Once the immune response and the mucosal barriers of the host become compromised, S. pneumoniae disseminates to other organs, causing a wide spectrum of diseases, which range from mild as otitis and sinusitis, to severe such as Invasive Pneumococcal Disease (IPD) [7,8,9]. IPD comprises bacteremic pneumonia, meningitis and sepsis and is considered an important cause of mortality in children and the elderly, representing approximately 12% of deaths every year worldwide [10]. A consistent decrease in the prevalence of pneumonia in children under five years old has been reported due to immunization programs [11], still 3.7 millions of severe episodes of pneumococcal disease and more than 300,000 deaths in children were estimated worldwide in 2015 [4]. Lack of effective vaccination programs in developing countries, serotype replacement of those not included in current vaccines and the continuous emergence of antibiotic resistance make S. pneumoniae a worldwide concern [12,13,14]
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