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2019-6-26 21:19:04


Magnen M, et al. Tissue kallikrein (KLK1) regulates alveolar macrophage apoptosis early in influenza virus infection. Am J Physiol Lung Cell Mol Physiol. 2019 Mar 25.
submited by kickingbird at Mar, 26, 2019 18:32 PM from Am J Physiol Lung Cell Mol Physiol. 2019 Mar 25.

Host cell proteases are involved in influenza pathogenesis. We examined the role of tissue kallikrein 1 (KLK1) by comparing wild-type (WT) and KLK1-deficient mice infected with influenza H3N2 virus. Levels of KLK1 in lung tissue and in bronchoalveolar lavage (BAL) fluid increased substantially during infection. KLK1 did not promote virus infectivity despite its trypsin-like activity but it did decrease the initial virus load. We examined two cell types involved in the early control of pathogen infections, alveolar macrophages (AMs) and natural killer (NK) cells, to learn more about the antiviral action of KLK1. Inactivating the Klk1 gene or treating WT mice with an anti-KLK1 monoclonal antibody to remove KLK1 activity accelerated the initial virus-induced apoptotic depletion of AMs. Intranasal instillation of deficient mice with recombinant KLK1 (rKLK1) reversed the phenotype. Levels of GM-CSF in infected BAL fluid were significantly lower in KLK1-deficient mice than in WT mice. Treating lung epithelial cells with rKLK1 increased secretion of this factor known to enhance AM resistance to pathogen-induced apoptosis. The recruitment of NK cells to the airspaces peaked 3 days after infection in WT mice, but not in KLK1-deficient mice, as did increases in several NK-attracting chemokines (CCL2, CCL3, CCL5 and CXCL10) in BAL. COPD patients are highly susceptible to viral infection and we observed that the KLK1 mRNA levels decreased with increasing COPD severity. Our findings indicate that KLK1 intervenes early in the antiviral defense modulating the severity of influenza infection. Decreased KLK1 expression in COPD patients could contribute to worsen influenza.

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