Immune modulation to improve survival of viral pneumonia in mice

Shradha Wali, Jose R. Flores, Ana M. Jaramillo, David L. Goldblatt, Jezreel Pantaleón García, Michael J. Tuvim, Burton F. Dickey, Scott E. Evans

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Viral pneumonias remain global health threats, as exemplified in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, requiring novel treatment strategies both early and late in the disease process. We have reported that mice treated before or soon after infection with a combination of inhaled Toll-like receptor (TLR) 2/6 and 9 agonists (Pam2-ODN) are broadly protected against microbial pathogens including respiratory viruses, but the mechanisms remain incompletely understood. The objective of this study was to validate strategies for immune modulation in a preclinical model of viral pneumonia and determine their mechanisms. Mice were challenged with the Sendai paramyxovirus in the presence or absence of Pam2-ODN treatment. Virus burden and host immune responses were assessed to elucidate Pam2-ODN mechanisms of action and to identify additional opportunities for therapeutic intervention. Enhanced survival of Sendai virus pneumonia with Pam2-ODN treatment was associated with reductions in lung virus burden and with virus inactivation before internalization. We noted that mortality in sham-treated mice corresponded with CD81 T-cell lung inflammation on days 11-12 after virus challenge, after the viral burden had declined. Pam2-ODN blocked this injurious inflammation by minimizing virus burden. As an alternative intervention, depleting CD81 T cells 8 days after viral challenge also decreased mortality. Stimulation of local innate immunity within the lungs by TLR agonists early in disease or suppression of adaptive immunity by systemic CD81 T-cell depletion late in disease improves outcomes of viral pneumonia in mice. These data reveal opportunities for targeted immunomodulation to protect susceptible human subjects.

Original languageEnglish (US)
Pages (from-to)758-766
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume63
Issue number6
DOIs
StatePublished - Dec 2020

Keywords

  • CD8 T cells
  • Immunomodulation
  • Immunopathology
  • Inducible epithelial resistance
  • Viral pneumonia

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

MD Anderson CCSG core facilities

  • Flow Cytometry and Cellular Imaging Facility

Fingerprint

Dive into the research topics of 'Immune modulation to improve survival of viral pneumonia in mice'. Together they form a unique fingerprint.

Cite this