Macrophage and Dendritic Cell Activation and Polarization in Response to Infection.

Coccidioidomycosis is a fungal, respiratory disease caused by and . The host immune responses that define disease outcome during infection are largely unknown, although T helper responses are required. Adaptive immunity is influenced by innate immunity as antigen-presenting cells activate and educate adaptive responses. Macrophage and dendritic cell (DC) recognition of pathogen surface molecules are critical for clearance. We characterize the broad innate immune responses to by analyzing macrophage and dendritic cell responses to arthroconidia using avirulent, vaccine strain NR-166 (), developed from parental virulent strain C735. We developed a novel flow cytometry-based method to analyze macrophage phagocytosis to complement traditional image-scoring methods. Our study found that macrophage polarization is blocked at M0 phase and activation reduced, while DCs polarize into proinflammatory DC1s, but not anti-inflammatory DC2, following interaction with . However, DCs exhibit a contact-dependent reduced activation to as defined by co-expression of MHC-II and CD86. In vivo, only modest DC1/DC2 recruitment and activation was observed with avirulent infection. In conclusion, the vaccine strain recruited a mixed DC population in vivo, while in vitro data suggest active innate immune cell inhibition by .