Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection

Lipopolysaccharides 0301 basic medicine [SDV.IMM] Life Sciences [q-bio]/Immunology Neutrophils Respiratory System Mice, Transgenic Ligands 12. Responsible consumption Mice 03 medical and health sciences 0302 clinical medicine Orthomyxoviridae Infections Macrophages, Alveolar Animals Respiratory Tract Infections Mice, Inbred BALB C NF-kappa B Epithelial Cells Bacterial Infections 3. Good health Mice, Inbred C57BL Pseudomonas aeruginosa Brief Definitive Reports Cytokines Female Bronchoalveolar Lavage Fluid Flagellin
DOI: 10.1084/jem.20070891 Publication Date: 2008-01-29T01:54:41Z
ABSTRACT
The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-κB activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection.
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