Progranulin Decreases Susceptibility to Streptococcus pneumoniae in Influenza and Protects against Lethal Coinfection.

Progranulin Decreases Susceptibility to Streptococcus pneumoniae in Influenza and Protects against Lethal Coinfection.
J Immunol. 2019 Sep 13;:
Authors: Wang X, Yuan J, Wang H, Gan N, Zhang Q, Liu B, Wang J, Shu Z, Rao L, Gou X, Zhang H, Yin Y, Zhang X
Abstract
Streptococcus pneumoniae coinfection is a major cause of mortality in influenza pandemics. Growing evidence shows that uncontrolled immune response results in severe tissue damage and thereby promotes death in coinfection. Progranulin (PGRN) is widely expressed in immune and epithelial cells and exerts anti-inflammatory role in many diseases. We found that PGRN levels were significantly elevated in clinical influenza/S. pneumoniae-coinfected patients. C57BL/6 wild-type (WT) and PGRN-deficient (PGRN-/-) mice were infected with influenza virus PR8 and then superchallenged with S. pneumoniae serotype 19F. Coinfected PGRN-/- mice showed increased mortality and weight loss compared with WT mice. PGRN deficiency led to increased bacterial loads in lungs without altering influenza virus replication, suggesting a role of PGRN in decreasing postinfluenza susceptibility to S. pneumoniae coinfection. Administration of recombinant PGRN improved survival of WT and PGRN-/- mice in lethal coinfection. Additionally, loss of PGRN resulted in aggravated lung damage along with massive proinflammatory cytokine production and immune cell infiltration during coinfection. Endoplasmic reticulum stres...

Source: Journal of Immunology - September 12, 2019 Category: Allergy & Immunology Authors: Wang X, Yuan J, Wang H, Gan N, Zhang Q, Liu B, Wang J, Shu Z, Rao L, Gou X, Zhang H, Yin Y, Zhang X Tags: J Immunol Source Type: research