Immune checkpoints are suppressed during pregnancy following influenza A virus infection.

Vanders, RL; Gomez, HM; Daly, K; Wark, PA; Horvat, JC; Hansbro, PM

Immune checkpoints are suppressed during pregnancy following influenza A virus infection.

Vanders, RL Gomez, HM Daly, K Wark, PA Horvat, JC Hansbro, PM

Permalink

Publisher:: AMER PHYSIOLOGICAL SOC
Publication Type:: Journal Article
Citation:: Am J Physiol Lung Cell Mol Physiol, 2024, 327, (6), pp. L890-L904
Issue Date:: 2024-12-01

Closed Access

	Filename	Description	Size
	vanders-et-al-2024-immune-checkpoints-are-suppressed-during-pregnancy-following-influenza-a-virus-infection.pdf	Published version	4.33 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Vanders, RL
dc.contributor.author	Gomez, HM
dc.contributor.author	Daly, K
dc.contributor.author	Wark, PA
dc.contributor.author	Horvat, JC
dc.contributor.author	Hansbro, PM
dc.date.accessioned	2025-01-02T05:02:38Z
dc.date.available	2025-01-02T05:02:38Z
dc.date.issued	2024-12-01
dc.identifier.citation	Am J Physiol Lung Cell Mol Physiol, 2024, 327, (6), pp. L890-L904
dc.identifier.issn	1040-0605
dc.identifier.issn	1522-1504
dc.identifier.uri	http://hdl.handle.net/10453/182828
dc.description.abstract	Influenza A virus (IAV) infection is a major health risk during pregnancy. Although vaccination and antiviral agents are widely used and reduce IAV-induced symptoms, they are not sufficient to control IAV infections in pregnancy, especially during pandemics. Respiratory viruses like IAV exploit immune alterations that occur during pregnancy, including the upregulation of immune checkpoint proteins (ICPs) like programmed death ligand-1 (PDL1), programmed cell death receptor 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). We hypothesize that blocking expression of PDL1 on innate immune cells will improve maternal immunity following IAV infection. We used murine models of IAV infection during pregnancy with and without treatment with the immune checkpoint inhibitor (ICI), a-PDL1. Pregnant and nonpregnant mice were infected with mouse-adapted IAV (A/PR/8) and assessed at 3 days post infection (3 dpi). Lung cells were analyzed using flow cytometry. Lung mRNA expression of inflammatory and antiviral markers and histology was measured. Protein concentrations of inflammatory and antiviral markers, as well as viral titers were measured from lung bronchiolar lavage fluid (BALF). Lung function was also assessed. Following IAV infection, immune cells from pregnant mice had significant increases in the ICPs, PDL1, PD1, and CTLA4. a-PDL1 treatment effectively suppressed these ICPs and increased the activation marker, CD86. a-PDL1 treatment also reduced lung inflammatory cell infiltration and viral titers, increased antiviral responses, and improved lung function. Overall, IAV infection in pregnancy activates key inhibitory ICPs, leading to worsened disease outcomes. a-PDL1 treatment during IAV infection in pregnancy is an effective method to reduce ICP expression and improve overall immune cell responses.NEW & NOTEWORTHY Influenza infection worsens disease outcomes during pregnancy; however, treatment with anti-PDL1 can restore immune function during pregnancy.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER PHYSIOLOGICAL SOC
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1138004
dc.relation	http://purl.org/au-research/grants/nhmrc/1179092
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1138004
dc.relation.ispartof	Am J Physiol Lung Cell Mol Physiol
dc.relation.isbasedon	10.1152/ajplung.00391.2023
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0606 Physiology, 1116 Medical Physiology
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3208 Medical physiology
dc.subject.mesh	Animals
dc.subject.mesh	Female
dc.subject.mesh	Pregnancy
dc.subject.mesh	Mice
dc.subject.mesh	Orthomyxoviridae Infections
dc.subject.mesh	Influenza A virus
dc.subject.mesh	B7-H1 Antigen
dc.subject.mesh	Pregnancy Complications, Infectious
dc.subject.mesh	Lung
dc.subject.mesh	CTLA-4 Antigen
dc.subject.mesh	Programmed Cell Death 1 Receptor
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Immune Checkpoint Inhibitors
dc.subject.mesh	Immune Checkpoint Proteins
dc.subject.mesh	Lung
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice
dc.subject.mesh	Influenza A virus
dc.subject.mesh	Pregnancy Complications, Infectious
dc.subject.mesh	Orthomyxoviridae Infections
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	CTLA-4 Antigen
dc.subject.mesh	Programmed Cell Death 1 Receptor
dc.subject.mesh	B7-H1 Antigen
dc.subject.mesh	Immune Checkpoint Inhibitors
dc.subject.mesh	Immune Checkpoint Proteins
dc.subject.mesh	Animals
dc.subject.mesh	Female
dc.subject.mesh	Pregnancy
dc.subject.mesh	Mice
dc.subject.mesh	Orthomyxoviridae Infections
dc.subject.mesh	Influenza A virus
dc.subject.mesh	B7-H1 Antigen
dc.subject.mesh	Pregnancy Complications, Infectious
dc.subject.mesh	Lung
dc.subject.mesh	CTLA-4 Antigen
dc.subject.mesh	Programmed Cell Death 1 Receptor
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Immune Checkpoint Inhibitors
dc.subject.mesh	Immune Checkpoint Proteins
dc.title	Immune checkpoints are suppressed during pregnancy following influenza A virus infection.
dc.type	Journal Article
utslib.citation.volume	327
utslib.location.activity	United States
utslib.for	0606 Physiology
utslib.for	1116 Medical Physiology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)/Australian Institute for Microbiology & Infection (AIMI) Associate Members
utslib.copyright.status	closed_access	*
dc.date.updated	2025-01-02T05:01:22Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	327
utslib.citation.issue	6

Abstract:

Influenza A virus (IAV) infection is a major health risk during pregnancy. Although vaccination and antiviral agents are widely used and reduce IAV-induced symptoms, they are not sufficient to control IAV infections in pregnancy, especially during pandemics. Respiratory viruses like IAV exploit immune alterations that occur during pregnancy, including the upregulation of immune checkpoint proteins (ICPs) like programmed death ligand-1 (PDL1), programmed cell death receptor 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). We hypothesize that blocking expression of PDL1 on innate immune cells will improve maternal immunity following IAV infection. We used murine models of IAV infection during pregnancy with and without treatment with the immune checkpoint inhibitor (ICI), a-PDL1. Pregnant and nonpregnant mice were infected with mouse-adapted IAV (A/PR/8) and assessed at 3 days post infection (3 dpi). Lung cells were analyzed using flow cytometry. Lung mRNA expression of inflammatory and antiviral markers and histology was measured. Protein concentrations of inflammatory and antiviral markers, as well as viral titers were measured from lung bronchiolar lavage fluid (BALF). Lung function was also assessed. Following IAV infection, immune cells from pregnant mice had significant increases in the ICPs, PDL1, PD1, and CTLA4. a-PDL1 treatment effectively suppressed these ICPs and increased the activation marker, CD86. a-PDL1 treatment also reduced lung inflammatory cell infiltration and viral titers, increased antiviral responses, and improved lung function. Overall, IAV infection in pregnancy activates key inhibitory ICPs, leading to worsened disease outcomes. a-PDL1 treatment during IAV infection in pregnancy is an effective method to reduce ICP expression and improve overall immune cell responses.NEW & NOTEWORTHY Influenza infection worsens disease outcomes during pregnancy; however, treatment with anti-PDL1 can restore immune function during pregnancy.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/182828