tetano
Editor, Senior Moderator
Am J Pathol. 2013 Jul 4. pii: S0002-9440(13)00402-1. doi: 10.1016/j.ajpath.2013.05.016. [Epub ahead of print]
Marked Improvement of Severe Lung Immunopathology by Influenza-Associated Pneumococcal Superinfection Requires the Control of Both Bacterial Replication and Host Immune Responses.
Damjanovic D, Lai R, Jeyanathan M, Hogaboam CM, Xing Z.
Source
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Abstract
Bacterial superinfection and associated lung immunopathological characteristics are major contributors to hospitalizations and mortality after influenza. However, the underlying mechanisms and effective intervention strategies remain poorly defined. By using a model of influenza and pneumococcal superinfection, we found that dual-infected animals experienced rapid weight loss and succumbed to infection. Bacterial outgrowth, dysregulated cytokines, including KC and macrophage inflammatory protein 2, and severe lung neutrophilia and immunopathological characteristics were linked to the poor clinical outcome. In vivo neutralization of highly induced macrophage inflammatory protein 2 did not affect clinical outcome, bacterial loads, or lung immunopathological features. On the other hand, in vivo neutrophil depletion did not alter the clinical outcome and bacterial burden, although it moderately improved lung immunopathological features. Treatment with a bacteriostatic antibiotic, azithromycin, alone significantly improved clinical outcome and bacterial clearance, but it failed to reduce lung immunopathological characteristics. In comparison, treatment with a global inflammation inhibitor, dexamethasone, alone failed to alter clinical outcome, bacterial infection, and immunopathological features, despite its moderate reducing effects on neutrophilic and cytokine responses. In contrast, combined treatment with both azithromycin and dexamethasone best improved clinical outcome, bacterial clearance, lung cellular and cytokine responses, and immunopathological features. Our study suggests that marked improvement of clinical outcome and lung immunopathological features caused by bacterial superinfection requires the control of both bacterial infection and aberrant host immune responses. Our findings hold implications in clinical management for influenza-associated bacterial superinfections.
Copyright ? 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
23831294
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23831294
Marked Improvement of Severe Lung Immunopathology by Influenza-Associated Pneumococcal Superinfection Requires the Control of Both Bacterial Replication and Host Immune Responses.
Damjanovic D, Lai R, Jeyanathan M, Hogaboam CM, Xing Z.
Source
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Abstract
Bacterial superinfection and associated lung immunopathological characteristics are major contributors to hospitalizations and mortality after influenza. However, the underlying mechanisms and effective intervention strategies remain poorly defined. By using a model of influenza and pneumococcal superinfection, we found that dual-infected animals experienced rapid weight loss and succumbed to infection. Bacterial outgrowth, dysregulated cytokines, including KC and macrophage inflammatory protein 2, and severe lung neutrophilia and immunopathological characteristics were linked to the poor clinical outcome. In vivo neutralization of highly induced macrophage inflammatory protein 2 did not affect clinical outcome, bacterial loads, or lung immunopathological features. On the other hand, in vivo neutrophil depletion did not alter the clinical outcome and bacterial burden, although it moderately improved lung immunopathological features. Treatment with a bacteriostatic antibiotic, azithromycin, alone significantly improved clinical outcome and bacterial clearance, but it failed to reduce lung immunopathological characteristics. In comparison, treatment with a global inflammation inhibitor, dexamethasone, alone failed to alter clinical outcome, bacterial infection, and immunopathological features, despite its moderate reducing effects on neutrophilic and cytokine responses. In contrast, combined treatment with both azithromycin and dexamethasone best improved clinical outcome, bacterial clearance, lung cellular and cytokine responses, and immunopathological features. Our study suggests that marked improvement of clinical outcome and lung immunopathological features caused by bacterial superinfection requires the control of both bacterial infection and aberrant host immune responses. Our findings hold implications in clinical management for influenza-associated bacterial superinfections.
Copyright ? 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
23831294
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23831294