1565. Recognition of Coccidioides Endospores and Spherules by Individual Human Neutrophils
Session: Poster Abstract Session: Microbial and Host Genetic Factors in Disease
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C

Background:

"Valley fever" (coccidioidomycosis) is an infectious disease caused by parasitic forms of the dimorphic fungi Coccidioides spp. in mammalian hosts in the southwestern United States and in Central and South America. The disease has been known for more than a century; however, there currently is no vaccine or cure.

Methods:

Taking a fresh look at the innate host defense and at possible microbial strategies to evade immune recognition, we examine one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. Our single-live-cell/single-target approach is based on dual-micropipette aspiration and enables us to maneuver a Coccidioides endospore or spherule into close proximity of, or physical contact with, an initially quiescent, non-adherent neutrophil. For each studied pair of cell and fungal particle, we visualize and analyze separately the time courses of chemotaxis, adhesion, and phagocytosis, as well as their mutual interplay.

Results:

Employing the neutrophil morphology as an ultrasensitive “biosensor” of chemoattractants like C5a, we find that individual Coccidioides particles can induce the formation of complement-mediated, chemotactic pseudopods by neutrophils from a distance of 5-15 µm. Following contact, neutrophils (in the presence of autologous serum) vigorously attack and phagocytose Coccidioides endospores, and exhibit frustrated phagocytosis of the larger spherules. Whereas the neutrophil responses to Coccidioides and other yeast-like fungal particles are similar, these interactions with fungal targets differ significantly from the neutrophil behavior during encounters with purely antibody-coated beads. Intriguingly, we also find that a small subpopulation of endospores are able to evade recognition by human neutrophils, presumably due to a thicker-than-usual "capsule" of extracellular matrix surrounding the particles with resultant antigenic masking.

Conclusion:

Our approach will assist future studies in establishing to what extent such capsules contribute to the virulent potential of Coccidioides and other microbes.

PMNvsCocciEndoAndSpherule.jpg

 

Volkmar Heinrich, PhD1, Cheng-Yuk Lee, PhD1, Demosthenes Pappagianis, MD, PhD2 and George R. Thompson III, MD3, (1)Biomedical Engineering, University of California - Davis, Davis, CA, (2)University of California School of Medicine, Davis, CA, (3)Medical Microbiology and Immunology, University of California-Davis, Davis, CA

Disclosures:

V. Heinrich, None

C. Y. Lee, None

D. Pappagianis, None

G. R. Thompson III, None

Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.