%0 Journal Article
%T MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2
%A Emma S. Winkler
%A Glennys V. Reynoso
%A Heather D. Hickman
%A Mary K. McCarthy
%A Matthias Mack
%A Michael S. Diamond
%A Thomas E. Morrison
%J -
%D 2020
%R 10.1371/journal.ppat.1008292
%X 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
%K Monocytes
%K Chikungunya infection
%K Neutrophils
%K B cells
%K Pathogens
%K Lymphocytes
%K Chikungunya virus
%K Flow cytometry
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008292