Cooperation of immune regulators Tollip and surfactant protein A inhibits influenza A virus infection in mice.

Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101090633 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-993X (Electronic) Linking ISSN: 14659921 NLM ISO Abbreviation: Respir Res Subsets: MEDLINE

Publication: 2001- : London : BioMed Central Ltd.
Original Publication: London : Current Science Ltd., c2000-

Mice, Knockout* ; Pulmonary Surfactant-Associated Protein A*/metabolism ; Pulmonary Surfactant-Associated Protein A*/genetics ; Orthomyxoviridae Infections*/immunology ; Orthomyxoviridae Infections*/virology ; Orthomyxoviridae Infections*/metabolism ; Influenza A virus*/immunology ; Mice, Inbred C57BL*; Animals ; Mice ; Intracellular Signaling Peptides and Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Lung/immunology ; Lung/metabolism ; Lung/virology

Background: Influenza A virus (IAV) infection is a significant risk factor for respiratory diseases, but the host defense mechanisms against IAV remain to be defined. Immune regulators such as surfactant protein A (SP-A) and Toll-interacting protein (Tollip) have been shown to be involved in IAV infection, but whether SP-A and Tollip cooperate in more effective host defense against IAV infection has not been investigated.
Methods: Wild-type (WT), Tollip knockout (KO), SP-A KO, and Tollip/SP-A double KO (dKO) mice were infected with IAV for four days. Lung macrophages were isolated for bulk RNA sequencing. Precision-cut lung slices (PCLS) from WT and dKO mice were pre-treated with SP-A and then infected with IAV for 48 h.
Results: Viral load was significantly increased in bronchoalveolar lavage (BAL) fluid of dKO mice compared to all other strains of mice. dKO mice had significantly less recruitment of neutrophils into the lung compared to Tollip KO mice. SP-A treatment of PCLS enhanced expression of TNF and reduced viral load in dKO mouse lung tissue. Pathway analysis of bulk RNA sequencing data suggests that macrophages from IAV-infected dKO mice reduced expression of genes involved in neutrophil recruitment, IL-17 signaling, and Toll-like receptor signaling.
Conclusions: Our data suggests that both Tollip and SP-A are essential for the lung to exert more effective innate defense against IAV infection.
(© 2024. The Author(s).)

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U19 AI125357 United States AI NIAID NIH HHS; U19AI125357 United States NH NIH HHS

Keywords: Influenza A virus; Neutrophilic inflammation; Surfactant protein A; Tollip

0 (Pulmonary Surfactant-Associated Protein A)
0 (Intracellular Signaling Peptides and Proteins)

Date Created: 20240503 Date Completed: 20240503 Latest Revision: 20240617

20240617

PMC11068576

10.1186/s12931-024-02820-3

38702733