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

McCarthy, Mary K.; Reynoso, Glennys V.; Winkler, Emma S.; Mack, Matthias; Diamond, Michael S.; Hickman, Heather D.; Morrison, Thomas E.

Pathogenic CHIKV infection results in decreased accumulation of naïve lymphocytes and extensive lymphocyte relocalization in the dLN [23] . Because monocyte and neutrophil infiltration of the dLN preceded the disruption of lymphocyte populations (Fig 1 and [23] ), we hypothesized that accumulation of myeloid cells in the dLN might disrupt its architecture. To prevent the early influx of monocytes and neutrophils into the dLN, we treated mice with a single dose of anti-Gr-1 monoclonal antibody (mAb) the day before inoculation with pathogenic CHIKV, which effectively depleted monocytes and neutrophils from the circulation (Fig 2A-2C ) and the dLN (Fig 2D-2F) . Remarkably, a single anti-Gr-1 mAb treatment prior to pathogenic CHIKV infection restored total cell numbers at 5 dpi in the dLN to levels nearly equivalent to those detected during acutely cleared CHIKV infection (Fig 2G) , an effect that was due principally to changes in B and CD4 + T cell numbers (Fig 2H and 2I) . CD8 + T cell numbers in anti-Gr-1-treated mice remained lower than in mice infected with the attenuated CHIKV strain (Fig 2J) . The failure to fully restore CD8 + T cell numbers may reflect some effect of the anti-Gr-1 mAb on CD8 + T cells, some of which express Gr-1 upon activation [27] . Depletion of monocytes and neutrophils prior to attenuated CHIKV infection did not affect total cell numbers in the dLN at 5 dpi (S3 Fig) .