Author ORCID Identifier

0009-0003-0005-8173

Date of Graduation

5-2026

Document Type

Thesis (MS)

Program Affiliation

Biochemistry and Cell Biology

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Scott E. Evans

Committee Member

Joseph L. Alcorn, Jr., PhD

Committee Member

Seyed Javed M. Moghaddam, M.D.

Committee Member

Tingting W. Mills, PhD.

Committee Member

Xiaoyi Yuan, PhD.

Abstract

Lower respiratory tract infections (LRTIs) remain a leading cause of morbidity and mortality worldwide, with the immunocompromised patient population at greatest risk. In the setting of emerging infections and escalating antimicrobial resistance, there is an urgent need for novel strategies to protect susceptible patients against these infections. Our lab has previously demonstrated that inhaled treatment with a specific dyad of synthetic pattern recognition receptor (PRR) agonists, Pam2CSK4 and ODN M362 (referred to as “Pam2ODN”), can reduce the pathogen burden and improve mouse survival of pneumonia challenges. We have shown that protection against bacterial pathogens requires STAT3 activation. We hypothesize here that STAT3 activation is also required for Pam2ODN-induced protection against the influenza A virus (IAV).

In our in-vitro model, human bronchial epithelial cells (HBEC3-kt) were treated with STAT3 inhibitor C188-9 prior to receiving Pam2ODN treatment, and then were infected with IAV. We performed quantitative-PCR probing for Iav nucleoprotein (NP) and observed that cells with STAT3 inhibition and Pam2ODN treatment had elevated IAV nucleoprotein (NP) burden compared to cells treated with Pam2ODN only.  Furthermore, we challenged lung epithelium-specific STAT3 deletant mice and their floxed littermates with IAV following treatment with PBS or Pam2ODN. We observed here that Pam2ODN-treated STAT3-deletant mice had a significantly lower survival than Pam2ODN-treated floxed mice. Taken together, findings from both our in vivo and in vitro models suggest that STAT3 deficiency abrogates Pam2ODN’s protection against IAV thus, confirming our hypothesis that STAT3 is required for Pam2ODN induced protection against influenza A.

Keywords

STAT3, influenza A, lung epithelium

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Available for download on Friday, April 23, 2027

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