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 (dx.doi.org/10.1.... 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 bme.ucdavis.edu....
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.

[@yanosaubron8172]

Idk why but the adhesion test is just hilarious. It’s just... *boop* and the antigen sticks to them XD

[@alveronandreas4483]

This time we need the big guy (macrophages)

[@parus6422]

I dont know man...you need to bomb that with like Eos or somthing.

[@thecakeisalie1885]

We need the small guys (Antibodys)

[@LeBacon]

@@thecakeisalie1885 sir yes sir!

[@thecakeisalie1885]

That is the 99th time of a bacteria infection

[@LeBacon]

@@thecakeisalie1885 what?

[@kessu83]

NAture is unbelievable...how such small organism can be so amazingly complex and effective.

[@SaeedGOONER]

Amazing stuff! I showed this video to my students to show them chemotaxis and phagocytosis :) thank you for your work and your upload.

[@HeinrichLab]

Thank you very much for your encouraging feedback! Yes, videos of immune cells in action tend to make teaching immunology a lot easier.

[@heroe666111]

Wow.. Awesome video. Thank you. I know someone that unfortunately tested positive for Coccidiodomycosis. Caused very bad pneumonia. Now Fluconazole meds started for 3 months.

[@Opti-Mystic]

Excellent footage. Many thanks Sir

[@HeinrichLab]

Glad you enjoyed it!

[@TheEchoeman]

I love you neutrophils!

[@thecakeisalie1885]

Neutrophil:tries to swallow him The thing:haha Neutrophil:Ur fat

[@erwin757]

Do the neutrophils have standard antigen adhesion for most fungi? And is this because fungi consist of standard proteins antigens?

[@HeinrichLab]

The fungi's outer shell is made of sugars that are recognized by the host's complement system and antibodies in this case. After those markers (present in the host serum) coat a fungal particle, host cells adhere via their complement and antibody receptors. (Other fungi actually have "learned" to make shells that prevent them from being recognized in this way, for example Cryptococcus sp.)

[@TP-mv6en]

how does the chemotaxis work?

[@comradecockatoo3558]

How did you “hold” the cells in place?

[@HeinrichLab]

They're held with gentle suction pressure at the tip of glass micropipettes; see kzbin.info/www/bejne/imWue3d_mN1jadk.

[@cyberianbearhub]

How are they sensing the direction of cocci? No eyes the what?

[@pietajunior3437]

It's literally said in the video - chemotaxis

[@cyberianbearhub]

@@pietajunior3437 yess chemotaxis but how neutrophile is sensing the position of cocci without any contact? (At test part of video)

[@pietajunior3437]

@@cyberianbearhub Cocci produces certain chemicals that the neutrophil recognizes as a threat. If those chemicals are coming from one direction, it will extend in that direction.

[@HeinrichLab]

It's actually even cooler than that. The chemicals whose concentration gradient tells the cell where the "target" is derive from the serum of the host organism (human in this case) rather than the pathogen. But they require contact with the pathogen surface to produce (and then release) the peptides that activate and guide nearby host cells to the pathogen. These proteins belong to the group of complement proteins (or fragments thereof). A short explanation is included in the video at kzbin.info/www/bejne/oma3lIuLm62qnJY.

[@thecakeisalie1885]

The neutrophil:Target locked

[@amauta5]

Thank you for the video.

[@hayleereisinger8445]

Were these taken using TEM?

[@HeinrichLab]

These videos are made from image sequences recorded on an optical microscope (not TEM).

[@sylviahernandez8279]

What did it look like when they were done?

[@HeinrichLab]

Good question! Frustrated phagocytosis of the large spherules continues for a while, but the neutrophils cannot fully surround them. Other neutrophils might move in to help; see also doi.org/10.1371/journal.pone.0129522.g006. We don't usually watch these encounters for much longer though.

[@Liberperlo]

@@HeinrichLab feel sorry for the neutrophil!

[@Polaris97]

See how neutrophil went crazy after it sense coccidioides

[@ahmetyahsi3391]

Omg! That is awesome my god!

[@JDoe001]

Freaking “A”! It’s like watching a snake eat a horse!

[@gajanankatkar3398]

wowww very nice...

[@Daktangle]

Hungry hungry Neutrophils.