One-hit wonder: Late after burn injury,granulocytes can clear one bacterial infection but cannot control a subsequent infection |
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| Institution: | 1. Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;2. Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;3. Marsico Lung Institute/Cystic Fibrosis Research Center, USA;4. Jaycee Burn Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;1. Montefiore Institute for Minimally Invasive Surgery, Montefiore Medical Center, Bronx, New York;2. Albert Einstein College of Medicine, Department of Surgery, Bronx, New York;1. Association of Dutch Burn Centres, Maasstad Hospital, Rotterdam, The Netherlands;2. Department of Plastic, Reconstructive and Hand Surgery, Amsterdam Movement Sciences, VU University Medical Centre, Amsterdam, The Netherlands;1. Department of Plastic, Reconstructive and Hand Surgery, Amsterdam Movement Sciences, VU University Medical Centre, Amsterdam, The Netherlands;2. Association of Dutch Burn Centers, Red Cross Hospital, Beverwijk, The Netherlands;1. Association of Dutch Burn Centres, Maasstad Hospital, Rotterdam, The Netherlands;2. Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands;3. Department of Trauma Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands;1. The Scar Free Foundation Birmingham Centre for Burns Research, Birmingham, UK;2. Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK;3. Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham B15 2WB, UK;1. The Scar Free Foundation Birmingham Centre for Burns Research, Birmingham, UK;2. NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS Foundation Trust, UK;3. Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham B15 2WB, UK |
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| Abstract: | ObjectiveBurn injury induces an acute hyperactive immune response followed by a chronic immune dysregulation that leaves those afflicted susceptible to multiple secondary infections. Many murine models are able to recapitulate the acute immune response to burn injury, yet few models are able to recapitulate long-term immune suppression and thus chronic susceptibility to bacterial infections seen in burn patients. This has hindered the field, making evaluation of the mechanisms responsible for these susceptibilities difficult to study. Herein we describe a novel mouse model of burn injury that promotes chronic immune suppression allowing for susceptibility to primary and secondary infections and thus allows for the evaluation of associated mechanisms.MethodsC57Bl/6 mice receiving a full-thickness contact burn were infected with Pseudomonas aeruginosa 14 days (primary infection) and/or 17 days (secondary infection) after burn or sham injury. The survival, pulmonary and systemic bacterial load as well as frequency and function of innate immune cells (neutrophils and macrophages) were evaluated.ResultsFollowing secondary infection, burn mice were less effective in clearance of bacteria compared to sham injured or burn mice following a primary infection. Following secondary infection both neutrophils and macrophages recruited to the airways exhibited reduced production of anti-bacterial reactive oxygen and nitrogen species and the pro-inflammatory cytokineIL-12 while macrophages demonstrated increased expression of the anti-inflammatory cytokine interleukin-10 compared to those from sham burned mice and/or burn mice receiving a primary infection. In addition the BALF from these mice contained significantly higher level so of the anti-inflammatory cytokine IL-4 compared to those from sham burned mice and/or burn mice receiving a primary infection.ConclusionsBurn-mediated protection from infection is transient, with a secondary infection inducing immune protection to collapse. Repeated infection leads to increased neutrophil and macrophage numbers in the lungs late after burn injury, with diminished innate immune cell function and an increased anti-inflammatory cytokine environment. |
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| Keywords: | Burn Granulocytes Pseudomonas Neutrophils Macrophages |
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