Co-infection with Streptococcus pneumoniae modulates the B cell response to influenza virus.

J Virol. 2014 Aug 6. pii: JVI.01833-14. [Epub ahead of print]

Co-infection with Streptococcus pneumoniae modulates the B cell response to influenza virus.

Wolf AI1, Strauman MC1, Mozdzanowska K1, Whittle JR2, Williams KL1, Sharpe AH3, Weiser JN4, Caton AJ1, Hensley SE1, Erikson J5.

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Abstract

Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae (Sp) and are the basis of effective vaccines. Sequential or overlapping co-infections with both pathogens are common, yet the impact of co-infection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in IAV-Sp co-infected mice and that this response differs depending on the order of pathogen exposure. In mice exposed to Sp prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4+ T follicular helper (TFH) cell numbers. In contrast, secondary Sp infection exaggerates early anti-viral antibody secreting cell formation, and at later times GCs, TFH cells and anti-viral serum IgG are elevated. Mice exposed to Sp prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs, and exhibit reduced anti-viral serum IgG with diminished virus-neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective anti-viral Abs and may partially explain the differential susceptibility and disease outcomes to IAV infection in humans.

IMPORTANCE:

Respiratory tract co-infections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how Sp co-infection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID: 25100838 [PubMed - as supplied by publisher]