Cathepsin L Helps to Defend Mice from Infection with Influenza A.

Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL prote...

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Main Authors: Xiang Xu, John R Greenland, Jeffrey E Gotts, Michael A Matthay, George H Caughey
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5055332?pdf=render
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author Xiang Xu
John R Greenland
Jeffrey E Gotts
Michael A Matthay
George H Caughey
author_facet Xiang Xu
John R Greenland
Jeffrey E Gotts
Michael A Matthay
George H Caughey
author_sort Xiang Xu
collection DOAJ
description Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl-/- mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl+/+ mice. Lung inflammation in surviving infected mice peaked 14 days after initial infection, accompanied marked focal distal airway bronchiolization and epithelial metaplasia followed by desquamation and fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths occurred during the second week of infection in both groups of mice. In contrast to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather than polymorphonuclear. The histopathology of lung inflammation and remodeling in survivors was similar in Ctsl-/- and Ctsl+/+ mice, although Ctsl+/+ mice cleared immunoreactive virus sooner. Furthermore, Ctsl-/- mice had profound deficits in CD4+ lymphocytes before and after infection and weaker production of pathogen-specific IgG. Thus, CTSL appears to support innate as well as adaptive responses, which confer a survival advantage on mice infected with the orthomyxovirus influenza A.
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spelling doaj.art-a443385108de4852baad623a323f6e172022-12-22T02:46:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016450110.1371/journal.pone.0164501Cathepsin L Helps to Defend Mice from Infection with Influenza A.Xiang XuJohn R GreenlandJeffrey E GottsMichael A MatthayGeorge H CaugheyHost-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl-/- mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl+/+ mice. Lung inflammation in surviving infected mice peaked 14 days after initial infection, accompanied marked focal distal airway bronchiolization and epithelial metaplasia followed by desquamation and fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths occurred during the second week of infection in both groups of mice. In contrast to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather than polymorphonuclear. The histopathology of lung inflammation and remodeling in survivors was similar in Ctsl-/- and Ctsl+/+ mice, although Ctsl+/+ mice cleared immunoreactive virus sooner. Furthermore, Ctsl-/- mice had profound deficits in CD4+ lymphocytes before and after infection and weaker production of pathogen-specific IgG. Thus, CTSL appears to support innate as well as adaptive responses, which confer a survival advantage on mice infected with the orthomyxovirus influenza A.http://europepmc.org/articles/PMC5055332?pdf=render
spellingShingle Xiang Xu
John R Greenland
Jeffrey E Gotts
Michael A Matthay
George H Caughey
Cathepsin L Helps to Defend Mice from Infection with Influenza A.
PLoS ONE
title Cathepsin L Helps to Defend Mice from Infection with Influenza A.
title_full Cathepsin L Helps to Defend Mice from Infection with Influenza A.
title_fullStr Cathepsin L Helps to Defend Mice from Infection with Influenza A.
title_full_unstemmed Cathepsin L Helps to Defend Mice from Infection with Influenza A.
title_short Cathepsin L Helps to Defend Mice from Infection with Influenza A.
title_sort cathepsin l helps to defend mice from infection with influenza a
url http://europepmc.org/articles/PMC5055332?pdf=render
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AT georgehcaughey cathepsinlhelpstodefendmicefrominfectionwithinfluenzaa