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Silent neonatal influenza A virus infection primes systemic antimicrobial immunity

Summary

Infections with influenza A viruses (IAV) cause seasonal epidemics and global pandemics. The majority of these infections remain asymptomatic, especially among children below five years of age. Importantly, this is a time, when immunological imprinting takes place. Whether early-life infections with IAV affect the development of antimicrobial immunity is unknown. Using a preclinical mouse model, the authors of this article, led by Dorothee Viemann at the Center for Infection Research, University Würzburg, Germany, and in collaboration with GCIR member Professor Mirco Schmolke demonstrate that silent neonatal influenza infections have a remote beneficial impact on the later control of systemic juvenile-onset and adult-onset infections with an unrelated pathogen, Staphylococcus aureus, due to improved pathogen clearance and clinical resolution. Strategic vaccination with a live attenuated IAV vaccine elicited a similar protection phenotype. This phenotype is distinct from so called bacterial super infections in the respiratory tract when IAV enhances local colonization for S. aureus or Streptococcus.

Mechanistically, the IAV priming effect of systemic antimicrobial responses primarily targets functions of the developing innate immune system including increased antimicrobial plasma activity and enhanced phagocyte functions and antigen-presenting properties at mucosal sites. Their results suggest a long-term benefit from an exposure to IAV during the neonatal phase, which might be exploited by strategic vaccination against influenza early in life to enforce the host’s resistance to later bacterial infections.

Funding sources: Deutsche Forschungsgemeinschaft (DFG), DFG under Germany`s Excellence Strategy and the Swiss National Science Foundation.

Full article: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1072142/full

Why is it important?

Up to 5 million annual cases of acute respiratory infections and approximately 500,000 human deaths worldwide are attributable to influenza virus infections. Influenza virus infections in infants can cause a broad clinical spectrum, ranging from severe to mild respiratory illness to a probably underestimated number of non-respiratory and asymptomatic illnesses. However, knowledge of the long-term effects of neonatal influenza infections is rather limited.

Using mouse models of asymptomatic neonatal influenza infection and influenza vaccination, the authors of this article evaluated their impact on subsequent systemic infection by an unrelated pathogen, Staphylococcus aureus. The authors observed improved clearance of this pathogen in adolescence and adulthood after neonatal exposure to influenza virus. They also found that this was mainly due to a stimulatory effect of the influenza virus on innate antimicrobial immune functions. Evidence is provided that this activation effect is only achieved if the virus is present during the neonatal period, but not afterwards.

The next step is to know whether early respiratory stimulation with influenza virus would also protect against sepsis with other gram-positive and gram-negative bacteria.

24 Jan 2023

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