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.

Following infection or vaccination, innate immune cells are recruited to lymphoid tissues [5, [47] [48] [49] . Myeloid-derived cells can have suppressive effects on adaptive immunity, depending on the local inflammatory milieu. For example, monocytes recruited to the dLN of LCMVinfected mice co-localize with and deplete virus-specific B cells in the interfollicular area [5] . Here, we show that pathogenic, but not acutely cleared CHIKV, similarly induces rapid recruitment of monocytes and neutrophils to the dLN. During pathogenic CHIKV infection, recruited monocytes and neutrophils localized to the SCS and medullary sinuses, with some We previously observed that pathogenic CHIKV infection blunts the accumulation of lymphocytes in the dLN by impairing recruitment of naïve lymphocytes from the circulation [23] . Failure to recruit new lymphocytes was due to reduced function of high endothelial venules (HEVs) and decreased production of homeostatic chemokines. Preventing the early influx of monocytes and neutrophils into the dLN restored naïve lymphocyte recruitment, as the lymphocyte numbers in the dLN were uniformly increased. Moreover, preventing the influx of monocytes and neutrophils into the dLN improved organization of B cell follicles, the T cell area, and the B-T cell border. It remains to be determined whether these infiltrating myeloid cells directly also affect the function of HEVs or the production of homeostatic chemokines. Furthermore, monocyte and neutrophil depletion improved virus-specific B cell responses in the dLN, with more GC B cells and plasma cells generated. This improved GC formation is likely a downstream consequence of boosted lymphocyte numbers and less perturbed dLN organization earlier during infection.