Macrophage and Dendritic Cell Activation and Polarization in Response to <i>Coccidioides</i><i>posadasii</i> Infection

• Main Authors: Anh L. Diep, Susana Tejeda-Garibay, Nadia Miranda, Katrina K. Hoyer
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Journal of Fungi
• Subjects: <i>Coccidioides immitis</i>; <i>Coccidioides posadasii</i>; coccidioidomycosis; Valley fever; innate immunity; macrophage
• Online Access: https://www.mdpi.com/2309-608X/7/8/630

Coccidioidomycosis is a fungal, respiratory disease caused by <i>Coccidioides immitis</i> and <i>Coccidioides posadasii</i>. 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 <i>Coccidioides</i> clearance. We characterize the broad innate immune responses to <i>Coccidioides</i> by analyzing macrophage and dendritic cell responses to <i>Coccidioides</i> arthroconidia using avirulent, vaccine <i>Coccidioides</i> strain NR-166 (<i>Δcts2/Δard1/Δcts3</i>), 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 <i>Coccidioides</i>. However, DCs exhibit a contact-dependent reduced activation to <i>Coccidioides</i> as defined by co-expression of MHC-II and CD86. In vivo, only modest DC1/DC2 recruitment and activation was observed with avirulent <i>Coccidioides</i> infection. In conclusion, the vaccine <i>Coccidioides</i> strain recruited a mixed DC population in vivo, while in vitro data suggest active innate immune cell inhibition by <i>Coccidioides</i>.