Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages

Frontiers in Immunology

Immunology

Jonathan W. Yewdell¹  Hannah Atkins²  Todd M. Umstead³  Chintan K. Gandhi³  Linlin Yang³  Yan Chen³  Zoe E. Katz³  Eric Yau³  Zissis C. Chroneos⁴  E. Scott Halstead⁵ 

[1] Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States;Department of Comparative Medicine, Pennsylvania State University College of Medicine, PA, Hershey, United States;Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, PA, United States;Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, PA, United States;Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, United States;Department of Pediatrics, Division of Pediatric Critical Care Medicine, Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, PA, United States;

关键词: surfactant protein A;    macrophages;    influenza A virus;    lung;    collectin;   

DOI  :  10.3389/fimmu.2023.919800

 received in 2022-04-13, accepted in 2023-02-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

Influenza A virus infection (IAV) often leads to acute lung injury that impairs breathingand can lead to death, with disproportionate mortality in children and the elderly. Surfactant Protein A (SP-A) is a calcium-dependent opsonin that binds a variety of pathogens to help control pulmonary infections by alveolar macrophages. Alveolar macrophages play critical roles in host resistance and susceptibility to IAV infection. The effect of SP-A on IAV infection and antiviral response of macrophages, however, is not understood. Here, we report that SP-A attenuates IAV infection in a dose-dependent manner at the level of endosomal trafficking, resulting in infection delay in a model macrophage cell line. The ability of SP-A to suppress infection was independent of its glycosylation status. Binding of SP-A to hemagglutinin did not rely on the glycosylation status or sugar binding properties of either protein. Incubation of either macrophages or IAV with SP-A slowed endocytic uptake rate of IAV. SP-A interfered with binding to cell membrane and endosomal exit of the viral genome as indicated by experiments using isolated cell membranes, an antibody recognizing a pH-sensitive conformational epitope on hemagglutinin, and microscopy. Lack of SP-A in mice enhanced IFNβ expression, viral clearance and reduced mortality from IAV infection. These findings support the idea that IAV is an opportunistic pathogen that co-opts SP-A to evade host defense by alveolar macrophages. Our study highlights novel aspects of host-pathogen interactions that may lead to better understanding of the local mechanisms that shape activation of antiviral and inflammatory responses to viral infection in the lung.

【 授权许可】

Unknown   
Copyright © 2023 Yau, Yang, Chen, Umstead, Atkins, Katz, Yewdell, Gandhi, Halstead and Chroneos