Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity

Abstract

Tumor progression locus 2 (Tpl2) is a serine/threonine kinase that regulates the expression of inflammatory mediators in response to Toll-like receptors (TLR) and cytokine receptors. Global ablation of Tpl2 leads to severe disease in response to influenza A virus (IAV) infection, characterized by respiratory distress, and studies in bone marrow chimeric mice implicated Tpl2 in non-hematopoietic cells. Lung epithelial cells are primary targets and replicative niches of influenza viruses; however, the specific regulation of antiviral responses by Tpl2 within lung epithelial cells has not been investigated. Herein, we show that Tpl2 is basally expressed in primary airway epithelial cells and that its expression increases in both type I and type II airway epithelial cells (AECI and AECII) in response to influenza infection. We used Nkx2.1-cre to drive Tpl2 deletion within pulmonary epithelial cells to delineate epithelial cell-specific functions of Tpl2 during influenza infection in mice. Although modest increases in morbidity and mortality were attributed to cre-dependent deletion in lung epithelial cells, no alterations in host cytokine production or lung pathology were observed. In vitro, Tpl2 inhibition within the type I airway epithelial cell line, LET1, as well as genetic ablation in primary airway epithelial cells did not alter cytokine production. Overall, these findings establish that Tpl2-dependent defects in cells other than AECs are primarily responsible for the morbidity and mortality seen in influenza-infected mice with global Tpl2 ablation.

RETRACTED: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice

“…To isolate alveolar macrophages (AMs), BALF was collected, centrifuged and resuspended in DMEM containing 10% fetal bovine serum (FBS), and then allowed for 1 h adherence [ 34 ]. Type 1 (AT1) and type 2 (AT2) alveolar epithelial cells were isolated as previously described [ 35 ]. Briefly, euthanized mice were exsanguinated, and their lungs were perfused with sterile PBS until pink lungs turned to white.…”

Comprehensive Analysis of Soluble Mediator Profiles in Congenital CMV Infection Using an MCMV Model

“…In this regard, there is a study on cytokine/chemokine immune response that includes research based on an in-house multiplexed bead-based assay of amniotic fluid from HCMV-infected fetuses [ 38 ]. Several publications have used Luminex to detect cytokines in mouse tissue in the context of viral infection, including lung tissue in SARS-CoV-2 [ 64 ], influenza A virus [ 65 ], a mouse model of human respiratory syncytial virus infection [ 66 ], and also liver tissue in LCMV infection-induced viral hepatitis [ 67 ]. One limitation of our study is the use of a BAC-derived MCMV strain carrying a mutation in the MCK-2 viral-encoded chemokine, which is known to influence viral entry and immune infiltrates, as reviewed in [ 68 ].…”