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Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
Changes in Gut Microbiota Prior to Influenza A Virus Infection Do Not Affect Immune Responses in Pups or Juvenile
Eva Fuglsang1, Angela Pizzolla2, Lukasz Krych3
1Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Abstract:
Previous studies demonstrated that oral antibiotic (ABX) treatment prior to and during influenza A virus (IAV) infection of adult mice profoundly altered gut microbiota (GM) and was associated with increased susceptibility and impaired immunity to IAV. We examined the impact of ABX during critical times relevant to the establishment of GM in early life (using perinatal treatment of neonates and direct treatment of juvenile mice) and asked whether cessation of ABX treatment in early life had lasting effects on GM composition and anti-IAV immunity. ABX treatment significantly changed GM composition in juvenile mice and in ABX-treated dams. However, if ABX treatment ceased at the time of infection, neither neonates nor juvenile mice showed enhanced susceptibility to IAV, nor were major differences detected in cellular and humoral adaptive antiviral immunity. Thus, while ABX treatment alters GM diversity in early life, cessation and subsequent re-colonization correlates with effective immunity against IAV.
Insights
Antibiotic (ABX) use in early life alters gut microbiota (GM), but stopping ABX before influenza A virus (IAV) infection allows for immune recovery. Cessation and re-colonization promote effective anti-IAV immunity.
Area of Science:
- Microbiology
- Immunology
- Virology
Background:
- Previous research linked antibiotic (ABX) use during influenza A virus (IAV) infection in adult mice to altered gut microbiota (GM) and increased susceptibility.
- The impact of early-life ABX exposure on GM development and subsequent antiviral immunity remains less understood.
Purpose of the Study:
- To investigate the effects of perinatal and juvenile antibiotic treatment on gut microbiota composition.
- To determine if early-life antibiotic cessation influences susceptibility and immunity to influenza A virus infection.
- To assess the lasting impact on adaptive cellular and humoral antiviral immunity.
Main Methods:
- Antibiotic treatment was administered to neonatal mice (perinatal) and juvenile mice.
- Mice dams also received antibiotic treatment.
- Susceptibility to IAV, GM composition, and adaptive immune responses were analyzed following infection after antibiotic cessation.
Main Results:
- Antibiotic treatment significantly altered gut microbiota composition in juvenile mice and dams.
- However, mice whose antibiotic treatment ceased before IAV infection showed no increased susceptibility.
- No major differences in cellular and humoral adaptive antiviral immunity were detected in neonates or juveniles post-cessation.
Conclusions:
- While early-life antibiotic exposure alters gut microbiota, its cessation allows for effective immune recovery.
- Re-colonization of the gut microbiota following antibiotic cessation correlates with robust immunity against influenza A virus.
- These findings highlight the resilience of the immune system and gut microbiota following transient early-life antibiotic exposure.
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