First Author | Suresh MV | Year | 2019 |
Journal | JCI Insight | Volume | 4 |
Issue | 23 | PubMed ID | 31801911 |
Mgi Jnum | J:285250 | Mgi Id | MGI:6393384 |
Doi | 10.1172/jci.insight.131195 | Citation | Suresh MV, et al. (2019) TLR3 absence confers increased survival with improved macrophage activity against pneumonia. JCI Insight 4(23) |
abstractText | Toll-like receptor 3 (TLR3) is a pathogen recognition molecule associated with viral infection with double-stranded RNA (dsRNA) as its ligand. We evaluated the role of TLR3 in bacterial pneumonia using Klebsiella pneumoniae (KP). WT and TLR3-/- mice were subjected to a lethal model of KP. Alveolar macrophage polarization, bactericidal activity, and phagocytic capacity were compared. RNA-sequencing was performed on alveolar macrophages from the WT and TLR3-/- mice. Adoptive transfers of alveolar macrophages from TLR3-/- mice to WT mice with KP were evaluated for survival. Expression of TLR3 in postmortem human lung samples from patients who died from gram-negative pneumonia and pathological grading of pneumonitis was determined. Mortality was significantly lower in TLR3-/-, and survival improved in WT mice following antibody neutralization of TLR3 and with TLR3/dsRNA complex inhibitor. Alveolar macrophages from TLR3-/- mice demonstrated increased bactericidal and phagocytic capacity. RNA-sequencing showed an increased production of chemokines in TLR3-/- mice. Adoptive transfer of alveolar macrophages from the TLR3-/- mice restored the survival in WT mice. Human lung samples demonstrated a good correlation between the grade of pneumonitis and TLR3 expression. These data represent a paradigm shift in understanding the mechanistic role of TLR3 in bacterial pneumonia. |