Metformin Attenuates Inflammatory Responses and Enhances Antibody Production in an Acute Pneumonia Model of Streptococcus pneumoniae

Frontiers in Aging

Sunil K. Ahuja²  Audrey C. Anderson³  Chang-Jui Chen³  Alvaro G. Moreira⁶  Caitlyn Winter⁶  Noemi Borsa⁷  Sarah M. Bandy⁸  Cody A. Black⁸  Raymond Benavides⁸  Alexander Shaffer⁹  Marcos I. Restrepo⁹  Gabrielyd Hastings⁹  Cecilia Hinojosa⁹  Grace C. Lee^1,11 

[1] 0Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States;1Department of Microbiology, Immunology and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States;College of Pharmacy, The University of Texas at Austin, Austin, TX, United States;Department Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States;Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Department of Pediatrics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States;Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States;South Texas Veterans Health Care System, San Antonio, TX, United States;The Foundation for Advancing Veterans’ Health Research, San Antonio, TX, United States;Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States;

关键词: Streptococcus pneumoniae;    vaccine response;    metformin;    aging;    pneumonia;   

DOI  :  10.3389/fragi.2022.736835

来源: DOAJ

【 摘 要 】

Metformin may potentially reverse various age-related conditions; however, it is unclear whether metformin can also mitigate or delay the deterioration of immunological resilience that occurs in the context of infections that are commonly observed in older persons. We examined whether metformin promotes the preservation of immunological resilience in an acute S. pneumoniae (SPN) infection challenge in young adult mice. Mice were fed metformin (MET-alone) or standard chow (controls-alone) for 10 weeks prior to receiving intratracheal inoculation of SPN. A subset of each diet group received pneumococcal conjugate vaccine at week 6 (MET + PCV and control + PCV). Compared to controls-alone, MET-alone had significantly less infection-associated morbidity and attenuated inflammatory responses during acute SPN infection. Metformin lowered the expression of genes in the lungs related to inflammation as well as shorter lifespan in humans. This was accompanied by significantly lower levels of pro-inflammatory cytokines (e.g., IL6). MET + PCV vs. control + PCV manifested enhanced SPN anticapsular IgM and IgG levels. The levels of SPN IgM production negatively correlated with expression levels of genes linked to intestinal epithelial structure among MET + PCV vs. control + PCV groups. Correspondingly, the gut microbial composition of metformin-fed mice had a significantly higher abundance in the Verrucomicrobia, Akkermansia muciniphila, a species previously associated with beneficial effects on intestinal integrity and longevity. Together, these findings indicate metformin’s immunoprotective potential to protect against infection-associated declines in immunologic resilience.

【 授权许可】

Unknown