Anna J X Zhang1,2,3, Houshun Zhu4, Yanxia Chen1, Chuangen Li1, Can Li1, Hin Chu1,2,3, Leonardi Gozali1, Andrew C Y Lee1, Kelvin K W To1,2,3, Ivan F N Hung4, Kwok-Yung Yuen1,2,3. 1. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 2. Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China. 3. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China. 4. Department of Medicine, The University of Hong Kong, Hong Kong, China.
Abstract
BACKGROUND: Obesity is associated with increased severity of influenza infection. However, the underlying mechanism is largely unknown. METHODS: We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus. RESULTS: The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-β and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge compared with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice compared to that of lean mice postchallenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/β and cytokine genes at days 1 and 3 postinfection compared with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued until 6 days postchallenge ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival. CONCLUSIONS: Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.
BACKGROUND:Obesity is associated with increased severity of influenza infection. However, the underlying mechanism is largely unknown. METHODS: We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus. RESULTS: The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-β and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge compared with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice compared to that of lean mice postchallenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/β and cytokine genes at days 1 and 3 postinfection compared with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued until 6 days postchallenge ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival. CONCLUSIONS: Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.
Authors: Thais Fernanda de Campos Fraga-Silva; Sandra Regina Maruyama; Carlos Arterio Sorgi; Elisa Maria de Sousa Russo; Ana Paula Morais Fernandes; Cristina Ribeiro de Barros Cardoso; Lucia Helena Faccioli; Marcelo Dias-Baruffi; Vânia Luiza Deperon Bonato Journal: Front Immunol Date: 2021-01-29 Impact factor: 7.561
Authors: Elena Vianello; Elena Dozio; Francesco Bandera; Marco Froldi; Emanuele Micaglio; John Lamont; Lorenza Tacchini; Gerd Schmitz; Massimiliano Marco Corsi Romanelli Journal: Int J Mol Sci Date: 2020-01-14 Impact factor: 5.923