IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection

Xiaohui Wang; Kongyang Ma; Miao Chen; King-Hung Ko; Bo-Jian Zheng; Liwei Lu

doi:10.1371/journal.ppat.1005367

IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection

PLoS Pathog. 2016 Jan 6;12(1):e1005367. doi: 10.1371/journal.ppat.1005367. eCollection 2016 Jan.

Authors

Xiaohui Wang¹, Kongyang Ma¹, Miao Chen¹, King-Hung Ko¹, Bo-Jian Zheng¹, Liwei Lu¹

Affiliation

¹ Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.

Abstract

B-1 cells play a critical role in early protection during influenza infections by producing natural IgM antibodies. However, the underlying mechanisms involved in regulating this process are largely unknown. Here we found that during influenza infection pleural cavity B-1a cells rapidly infiltrated lungs, where they underwent plasmacytic differentiation with enhanced IgM production. This process was promoted by IL-17A signaling via induction of Blimp-1 expression and NF-κB activation in B-1a cells. Deficiency of IL-17A led to severely impaired B-1a-derived antibody production in the respiratory tract, resulting in a deficiency in viral clearance. Transfer of B-1a-derived natural antibodies rescued Il17a-/- mice from otherwise lethal infections. Together, we identify a critical function of IL-17A in promoting the plasmacytic differentiation of B-1a cells. Our findings provide new insights into the mechanisms underlying the regulation of pulmonary B-1a cell response against influenza infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes / cytology
B-Lymphocytes / immunology*
Cell Differentiation* / immunology
Chromatin Immunoprecipitation
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Expression Regulation / immunology
Immunity, Humoral / immunology
Influenza A Virus, H1N1 Subtype / immunology
Interleukin-17 / deficiency
Interleukin-17 / immunology*
Lymphocyte Activation / immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections / immunology*
Positive Regulatory Domain I-Binding Factor 1
Real-Time Polymerase Chain Reaction
Respiratory Tract Infections / immunology
Transcription Factors / biosynthesis*
Transcription Factors / immunology

Substances

Il17a protein, mouse
Interleukin-17
Prdm1 protein, mouse
Transcription Factors
Positive Regulatory Domain I-Binding Factor 1

Grants and funding

This work was supported by Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong SAR Government (No. 13121202), and National Major Research Program (No. 91442116), National Natural Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.