tetano
Editor, Senior Moderator
Front Immunol
. 2023 Mar 7;14:919800.
doi: 10.3389/fimmu.2023.919800. eCollection 2023.
Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages
Eric Yau[SUP] 1 [/SUP], Linlin Yang[SUP] 1 [/SUP], Yan Chen[SUP] 1 [/SUP], Todd M Umstead[SUP] 1 [/SUP], Hannah Atkins[SUP] 2 [/SUP], Zoe E Katz[SUP] 1 [/SUP], Jonathan W Yewdell[SUP] 3 [/SUP], Chintan K Gandhi[SUP] 1 [/SUP], E Scott Halstead[SUP] 4 [/SUP], Zissis C Chroneos[SUP] 1 5 [/SUP]
Affiliations
Abstract
Influenza A virus infection (IAV) often leads to acute lung injury that impairs breathing and 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.
Keywords: collectin; influenza A virus; lung; macrophages; surfactant protein A.
. 2023 Mar 7;14:919800.
doi: 10.3389/fimmu.2023.919800. eCollection 2023.
Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages
Eric Yau[SUP] 1 [/SUP], Linlin Yang[SUP] 1 [/SUP], Yan Chen[SUP] 1 [/SUP], Todd M Umstead[SUP] 1 [/SUP], Hannah Atkins[SUP] 2 [/SUP], Zoe E Katz[SUP] 1 [/SUP], Jonathan W Yewdell[SUP] 3 [/SUP], Chintan K Gandhi[SUP] 1 [/SUP], E Scott Halstead[SUP] 4 [/SUP], Zissis C Chroneos[SUP] 1 5 [/SUP]
Affiliations
- PMID: 36960051
- PMCID: PMC10028185
- DOI: 10.3389/fimmu.2023.919800
Abstract
Influenza A virus infection (IAV) often leads to acute lung injury that impairs breathing and 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.
Keywords: collectin; influenza A virus; lung; macrophages; surfactant protein A.