MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2

Autoři: Mary K. McCarthy aff001;  Glennys V. Reynoso aff002;  Emma S. Winkler aff003;  Matthias Mack aff004;  Michael S. Diamond aff003;  Heather D. Hickman aff002;  Thomas E. Morrison aff001
Působiště autorů: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America aff001;  Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Microbiology and Immunology, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, United States of America aff002;  Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America aff003;  Regensburg University Medical Center, Regensburg, Germany aff004;  Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America aff005;  Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America aff006;  The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri, United States of America aff007
Vyšlo v časopise: MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008292
Kategorie: Research Article


Humoral immune responses initiate in the lymph node draining the site of viral infection (dLN). Some viruses subvert LN B cell activation; however, our knowledge of viral hindrance of B cell responses of important human pathogens is lacking. Here, we define mechanisms whereby chikungunya virus (CHIKV), a mosquito-transmitted RNA virus that causes outbreaks of acute and chronic arthritis in humans, hinders dLN antiviral B cell responses. Infection of WT mice with pathogenic, but not acutely cleared CHIKV, induced MyD88-dependent recruitment of monocytes and neutrophils to the dLN. Blocking this influx improved lymphocyte accumulation, dLN organization, and CHIKV-specific B cell responses. Both inducible nitric oxide synthase (iNOS) and the phagocyte NADPH oxidase (Nox2) contributed to impaired dLN organization and function. Infiltrating monocytes expressed iNOS through a local IRF5- and IFNAR1-dependent pathway that was partially TLR7-dependent. Together, our data suggest that pathogenic CHIKV triggers the influx and activation of monocytes and neutrophils in the dLN that impairs virus-specific B cell responses.

Klíčová slova:

B cells – Flow cytometry – Chikungunya infection – Chikungunya virus – Lymphocytes – Monocytes – Neutrophils – Pathogens


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