Tu146 - Deficiency of TLR7 and IRF7 Impairs the Adaptive Immunity in Respiratory Viral Infection

Tuesday, June 24, 2025

6:00pm - 7:30pm East Coast USA Time

AN

Ana Karina Nisperuza Vidal, n/a

Graduate Student
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA and Tulane National Primate Research Center, Covington, LA, 70433, USA
New Orleans, Louisiana, United States
CW

Chenxiao Wang, M.S

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA and Tulane National Primate Research Center, Covington, LA, 70433, USA.
MA

Michaela J Allen

Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
CE

Calder R. Ellsworth, M.S

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA and Tulane National Primate Research Center, Covington, LA, 70433, USA.
MK

Mst Shamima Khatun

Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA, USA.
JK

Jay K Kolls

Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA, USA.
New Orleans, Florida, United States
DP

Derek A Pociask

Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA
XQ

Xuebin Qin, MD, PhD

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA and Tulane National Primate Research Center, Covington, LA, 70433, USA.

Abstract Text: Emerging clinical evidence suggests that the loss of X-linked recessive toll-like receptor 7 (TLR7) attributes to 2% of men under 60 years old with severe COVID-19, highlighting the critical pathogenic role of TLR7 in an innate immunity against SARS-CoV-2 infection. Previous studies also indicate that TLR7 contributes to adaptive immunity, namely antibody production. Recently, we reported that deficiency of Tlr7 and Irf7 in mice impairs innate and adaptive immunities against SARS-CoV2 infection associated with the reduced interferon (IFN) alpha and gamma levels (PMID: 39289468). However, the exact cellular and molecular mechanisms underlying TLR7-mediated signaling events that contribute to the immunity against the respiratory viral infection including Flu infection remain unclear. To dissect this question, we used the compound mice specifically deficient in IFN alpha receptors on dendritic cells (DC) (IFNARloxP+/+Cd11cCre+/-). We demonstrated SARS-CoV-2 -infected IFNARloxP+/+Cd11cCre+/- mice showed a tendency of lower anti-S IgG production than IFNARloxP+/+Cd11cCre-/- mice at 14-day post infection (DPI) (p=0.1000, n=3). Furthermore, upon challenge with influenza virus H1N1 A/PR/8/34, infected Irf7+/+ mice showed higher anti-Hemagglutinin (anti-HA) IgG levels than the infected Irf7−/− mice at 7 DPI (p=0.0292), and Tlr7+/+ mice had higher anti-HA IgG levels than the infected Tlr7−/− mice at 21 DPI (p=0.0413). Together, these findings highlight the important roles of TLR7, IRF7, and IFN in orchestrating effective antibody production during respiratory viral infections. Further understanding these molecular pathways will enhance our knowledge of immune responses and could provide therapeutic strategies against RNA viruses.