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.

Because TLR ligands can promote monocyte egress from the bone marrow to sites of infection [31] , we evaluated neutrophil and monocyte recruitment to the dLN of mice deficient in MyD88, the canonical adaptor for many TLRs and the interleukin-1 receptor (IL-1R) family [32] . Genetic deletion of MyD88 had minimal impact on the total number of cells in the dLN at 24 hpi (Fig 5G) . However, MyD88-dependent signals were required for and contributed to neutrophil (Fig 5H-5J ) and monocyte (Fig 5H, 5K and 5L) recruitment, respectively, to the dLN following pathogenic CHIKV infection. Mice treated with anti-IL-1R blocking mAb at the time of infection showed no change in total cells in the dLN compared with control IgGtreated mice (Fig 5M) , but had reduced neutrophils (percentage and total number; Fig 5N-5P) , indicating that the MyD88-IL-1R signaling axis regulates the rapid accumulation of neutrophils in the dLN during pathogenic CHIKV infection. In contrast, the percentage and total number of monocytes were unchanged in the anti-IL-1R-treated group compared with the IgG-treated group (Fig 5N, 5Q and 5R ). Together, these data demonstrate that in response to pathogenic CHIKV infection 1) type I IFN signaling inhibits and IL-1R signaling promotes, neutrophil recruitment to the dLN, and 2) IL-1R-independent, MyD88-dependent signal(s) promote the recruitment of monocytes to the dLN.