title: Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, California, United States of America.
authors.forename: Cheng-Yuk
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California Davis, Davis, California, United States of America; Department of Internal Medicine, Division of Infectious Diseases, University of California Davis Medical Center, Sacramento, California, United States of America.
authors.forename: George R
authors.initials: GR
authors.lastname: Thompson
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, California, United States of America.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Hastey
authors.affiliation: Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Hodge
authors.affiliation: Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Jennine M
authors.initials: JM
authors.lastname: Lunetta
authors.affiliation: Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Pappagianis
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, California, United States of America.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Heinrich
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003045:Coccidioides / Q000187:drug effects / Q000502:physiology*; D003047:Coccidioidomycosis / Q000382:microbiology; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology*; D010587:Phagocytosis / Q000187:drug effects; D013172:Spores, Fungal / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D000935:Antifungal Agents; D003165:Complement System Proteins