Human neutrophil versus Coccidioides (cause of Valley fever): Chemotaxis, adhesion, and phagocytosis

Coccidioides endospores and spherules draw strong chemotactic, adhesive, and phagocytic responses by individual human neutrophils.
This video presents an overview of a collaborative interdisciplinary study of the recognition of the pathogenic fungus Coccidioides posadasii (cause of Valley fever) by neutrophils. The study was published in PLOS ONE (http://dx.doi.org/10.1371/journal.pone.0129522). The paper's abstract is included below.
This study showcases how innovative concepts and approaches developed by bioengineers can provide new insight into the mechanisms of vital cellular behavior, and help us tackle scientific questions that are inaccessible to traditional biological methods. An authoritative overview of new insights gained from modern, interdisciplinary single-live-cell studies of phagocytosis can be found at http://bme.ucdavis.edu/heinrichlab/files/2015/11/Heinrich_BJ2015.pdf.

Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever) in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis) as well as upon contact (by serum-dependent adhesion and phagocytosis). This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

Видео Human neutrophil versus Coccidioides (cause of Valley fever): Chemotaxis, adhesion, and phagocytosis канала Heinrich Lab